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Guo XJ, He LW, Chang JQ, Su WN, Feng T, Gao YM, Wu YY, Zhao C, Rao JS. Epidural electrical stimulation combined with photobiomodulation restores hindlimb motor function in rats with thoracic spinal cord injury. Exp Neurol 2025; 385:115112. [PMID: 39667656 DOI: 10.1016/j.expneurol.2024.115112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 11/17/2024] [Accepted: 12/08/2024] [Indexed: 12/14/2024]
Abstract
Epidural electrical stimulation (EES) could restore motor function of paralyzed limbs of patients with spinal cord injury (SCI). However, its invasiveness limits its application in early stage of injury. Photobiomodulation (PBM) utilizes infrared light for percutaneous irradiation of the spinal cord to protect nerve tissue, delay muscle atrophy, and can be applied in early stage of SCI due to its non-invasiveness. This study tested the effect of the combination of EES and PBM on promoting motor function recovery in SCI rats. Severe contusion was induced at the T9 spinal segment in female rats, EES (applied to the L2 and S1 spinal cord segments) with treadmill training was conducted one week after the injury, and PBM percutaneous irradiation started at the injured segment on the day of surgery. In the third week post-injury, electromyographic and gait performance during training were recorded. Besides, the muscles of the hind limbs and the spinal cord on the caudal side of the injured segment were extracted. The results demonstrate that compared to the EES- or PBM-only group, this combined therapy led to several indicators returning to intact levels, including behavioral and electrophysiological, the gait patterns was also closer to intact rats. Additionally, the combined treatment group showed minimal muscle atrophy and maximal preservation of the injured spinal cord on the caudal side, with this histological improvement correlated with motor function recovery. Taken together, our results showed that this combined therapy was a more effective treatment for improving motor dysfunction after SCI which could protect the damaged spinal cord and promote the recovery of motor function in rats with SCI.
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Affiliation(s)
- Xiao-Jun Guo
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Le-Wei He
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Jia-Qi Chang
- School of Automation Science and Electrical Engineering, Beihang University, Beijing 100191, China
| | - Wen-Nan Su
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Ting Feng
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Yi-Meng Gao
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Yuan-Yuan Wu
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Can Zhao
- Institute of Rehabilitation Engineering, China Rehabilitation Science Institute, Beijing 100068, China.
| | - Jia-Sheng Rao
- Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
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Zhang X, Liu X, Li Q, Li C, Li X, Qian J, Li J, Li X. GsMTx-4 combined with exercise improves skeletal muscle structure and motor function in rats with spinal cord injury. PLoS One 2025; 20:e0317683. [PMID: 39841686 PMCID: PMC11753701 DOI: 10.1371/journal.pone.0317683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 01/02/2025] [Indexed: 01/30/2025] Open
Abstract
Motor dysfunction and muscle atrophy are typical symptoms of patients with spinal cord injury (SCI). Exercise training is a conventional physical therapy after SCI, but exercise intervention alone may have limited efficacy in reducing secondary injury and promoting nerve regeneration and functional remodeling. Our previous research found that intramedullary pressure after SCI is one of the key factors affecting functional prognosis. It has been reported that GsMTx-4, a specific blocker of the mechanosensitive ion channels Piezo1, can protect the integrity of the neuromuscular junction and promote nerve regeneration, and thus has the potential as a therapeutic agent for SCI. In this study, we observed the combined and separate therapeutic effect of GsMTx-4 and exercise on the structure of the soleus muscle and motor function in rats with SCI. At 42 days post-injury, compared with SCI rats, the Basso-Beattie-Bresnahan score (P = 0.0007) and Gait Symmetry (P = 0.0002) were significantly improved after combination therapy. On histology of rat soleus muscle, compared with SCI rats, the combined treatment significantly increased the wet weight ratio, muscle fiber cross-sectional area and acetylcholinesterase (all P<0.0001). On histology of rat spinal tissue, compared with SCI rats, the combined treatment significantly increased neuron counts and BDNF levels, and significantly reduced the percentage of TUNEL-positive cells (all P<0.0001). On physiology of rat soleus muscle, compared with SCI rats, the combined treatment increased the succinate dehydrogenase expression (P<0.0001), while the expression of α-glycerophosphate dehydrogenase (P<0.0001) and GDF8 protein (P = 0.0008) decreased. Results indicate the combination therapy effectively improves histopathology of spinal cord and soleus muscle in SCI rats, enhancing motor function. This study was conducted on animal models, it offers insights for SCI treatment, advancing understanding of lower limb muscle pathology post-SCI. Further research is needed for clinical validation in the future.
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Affiliation(s)
- Xin Zhang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Xinyu Liu
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Qianxi Li
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Chenyu Li
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Xinyan Li
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Jinghua Qian
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Jianjun Li
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Department of Spinal and Neural Function Reconstruction, China Rehabilitation Research Center, Beijing, China
- Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
- China Rehabilitation Science Institute, Beijing, China
- Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Xuemei Li
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
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Angelin LG, Carreño MNP, Otoch JP, de Resende JCF, Arévalo A, Motta-Teixeira LC, Seelaender MCL, Lepski G. Regeneration and Plasticity Induced by Epidural Stimulation in a Rodent Model of Spinal Cord Injury. Int J Mol Sci 2024; 25:9043. [PMID: 39201729 PMCID: PMC11354918 DOI: 10.3390/ijms25169043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/10/2024] [Accepted: 08/11/2024] [Indexed: 09/03/2024] Open
Abstract
Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin-eosin) and immunohistochemistry for NeuN, β-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for β-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in β-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury.
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Affiliation(s)
- Leonidas Gomes Angelin
- Laboratory of Medical Investigation, LIM26, Department of Experimental Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil
| | - Marcelo Nelson Páez Carreño
- Microelectronics and Materials Laboratory, Polytechnic School, University of Sao Paulo, Sao Paulo 05508-010, Brazil
| | - Jose Pinhata Otoch
- Laboratory of Medical Investigation, LIM26, Department of Experimental Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil
| | - Joyce Cristina Ferreira de Resende
- Laboratory of Medical Investigation, LIM26, Department of Experimental Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil
| | - Analía Arévalo
- Laboratory of Medical Investigation, LIM26, Department of Experimental Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil
| | - Lívia Clemente Motta-Teixeira
- Laboratory of Neuroplasticity and Behaviour, Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo 01221-020, Brazil;
| | - Marilia Cerqueira Leite Seelaender
- Laboratory of Medical Investigation, LIM26, Department of Experimental Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil
| | - Guilherme Lepski
- Laboratory of Medical Investigation, LIM26, Department of Experimental Surgery, Medical School, University of Sao Paulo, Sao Paulo 01246-903, Brazil
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Fu C, Lei Y, Liang L, Jiang J, Qin Y, Lao Y, Tan Z, Wang Y, Liu Q. Characterization of HSP90 expression and function following CNS injury. Neurosci Lett 2024; 836:137875. [PMID: 38857697 DOI: 10.1016/j.neulet.2024.137875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/26/2024] [Accepted: 06/07/2024] [Indexed: 06/12/2024]
Abstract
Spinal cord injury induces significant cellular stress responses. The Heat Shock Protein 90 (HSP90) plays a pivotal role as a molecular chaperone and is crucial for protein folding, stabilization, and cellular signaling pathways. Despite its important function in stress adaptation, the specific expression patterns and functional roles of HSP90 after nerve injury remain unclear. This study aimed to elucidate the expression dynamics and functional implications of HSP90 following central nervous system (CNS) injury. Using western blotting and immunohistochemical analyses, we observed upregulation of HSP90 expression in spinal cord tissues and within injured neurons in a spinal cord contusion injury model. Additionally, HSP90 was found to enhance neurite outgrowth in primary cortical neurons cultured in vitro. Furthermore, in a glutamate-induced neuronal injury model, the expression of HSP90 was up-regulated, and overexpression of HSP90 promoted neurite re-growth in damaged neurons. Overall, our findings highlight the critical involvement of HSP90 in the neural response to injury and offer valuable insights into potential therapeutic strategies for CNS repair.
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Affiliation(s)
- Chaohua Fu
- Department of Spine Surgery, Jiangmen Central Hospital, Guangdong Province, Jiangmen 529000, China; Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangdong Province, Guangzhou 510630, China
| | - Yaling Lei
- Department of Cell Biology, Jinan University, Guangzhou 510632, China
| | - Lin Liang
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangdong Province, Guangzhou 510630, China
| | - Jianxiong Jiang
- Department of Spine Surgery, Jiangmen Central Hospital, Guangdong Province, Jiangmen 529000, China
| | - Ying Qin
- Department of Spine Surgery, Jiangmen Central Hospital, Guangdong Province, Jiangmen 529000, China
| | - Yongbin Lao
- Department of Spine Surgery, Jiangmen Central Hospital, Guangdong Province, Jiangmen 529000, China
| | - Zhiwen Tan
- Department of Spine Surgery, Jiangmen Central Hospital, Guangdong Province, Jiangmen 529000, China
| | - Yuansheng Wang
- Department of Spine Surgery, Jiangmen Central Hospital, Guangdong Province, Jiangmen 529000, China.
| | - Qiuling Liu
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangdong Province, Guangzhou 510630, China.
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Coyoy-Salgado A, Segura-Uribe J, Salgado-Ceballos H, Castillo-Mendieta T, Sánchez-Torres S, Freyermuth-Trujillo X, Orozco-Barrios C, Orozco-Suarez S, Feria-Romero I, Pinto-Almazán R, Moralí de la Brena G, Guerra-Araiza C. Evaluating Sex Steroid Hormone Neuroprotection in Spinal Cord Injury in Animal Models: Is It Promising in the Clinic? Biomedicines 2024; 12:1478. [PMID: 39062051 PMCID: PMC11274729 DOI: 10.3390/biomedicines12071478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 06/11/2024] [Accepted: 06/26/2024] [Indexed: 07/28/2024] Open
Abstract
The primary mechanism of traumatic spinal cord injury (SCI) comprises the initial mechanical trauma due to the transmission of energy to the spinal cord, subsequent deformity, and persistent compression. The secondary mechanism of injury, which involves structures that remained undamaged after the initial trauma, triggers alterations in microvascular perfusion, the liberation of free radicals and neurotransmitters, lipid peroxidation, alteration in ionic concentrations, and the consequent cell death by necrosis and apoptosis. Research in the treatment of SCI has sought to develop early therapeutic interventions that mitigate the effects of these pathophysiological mechanisms. Clinical and experimental evidence has demonstrated the therapeutic benefits of sex-steroid hormone administration after traumatic brain injury and SCI. The administration of estradiol, progesterone, and testosterone has been associated with neuroprotective effects, better neurological recovery, and decreased mortality after SCI. This review evaluated evidence supporting hormone-related neuroprotection over SCI and the possible underlying mechanisms in animal models. As neuroprotection has been associated with signaling pathways, the effects of these hormones are observed on astrocytes and microglia, modulating the inflammatory response, cerebral blood flow, and metabolism, mediating glutamate excitotoxicity, and their antioxidant effects. Based on the current evidence, it is essential to analyze the benefit of sex steroid hormone therapy in the clinical management of patients with SCI.
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Affiliation(s)
- Angélica Coyoy-Salgado
- CONAHCyT-Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico;
| | - Julia Segura-Uribe
- Subdirección de Gestión de la Investigación, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City 06720, Mexico;
| | - Hermelinda Salgado-Ceballos
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (H.S.-C.); (T.C.-M.); (S.S.-T.); (S.O.-S.)
| | - Tzayaka Castillo-Mendieta
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (H.S.-C.); (T.C.-M.); (S.S.-T.); (S.O.-S.)
| | - Stephanie Sánchez-Torres
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (H.S.-C.); (T.C.-M.); (S.S.-T.); (S.O.-S.)
| | - Ximena Freyermuth-Trujillo
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (H.S.-C.); (T.C.-M.); (S.S.-T.); (S.O.-S.)
| | - Carlos Orozco-Barrios
- CONAHCyT-Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico;
| | - Sandra Orozco-Suarez
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (H.S.-C.); (T.C.-M.); (S.S.-T.); (S.O.-S.)
| | - Iris Feria-Romero
- Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (H.S.-C.); (T.C.-M.); (S.S.-T.); (S.O.-S.)
| | - Rodolfo Pinto-Almazán
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Mexico City 11340, Mexico
| | - Gabriela Moralí de la Brena
- Unidad de Investigación Médica en Farmacología, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
| | - Christian Guerra-Araiza
- Unidad de Investigación Médica en Farmacología, Hospital de Especialidades Dr. Bernardo Sepúlveda, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
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Li X, Ding Y, Haddad YW, Geng X. Greater Omentum: Multifaceted Interactions in Neurological Recovery and Disease Progression. Aging Dis 2024; 15:2381-2394. [PMID: 38421824 PMCID: PMC11567243 DOI: 10.14336/ad.2024.0213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 02/13/2024] [Indexed: 03/02/2024] Open
Abstract
The greater omentum, a unique anatomical structure composed of adipocytes, loose connective tissue, and a dense vascular network. Plays a pivotal role beyond its traditional understanding. It houses specialized immunological units known as 'Milky spots,' making it a key player in immune response. Moreover, the omentum's capacity to enhance tissue perfusion, absorb edema fluid, boost acetylcholine synthesis, and foster neuron repair have rendered it a topic of interest in the context of various diseases, especially neurological disorders. This review provides a comprehensive overview of the intricate anatomy and histology of the greater omentum, casting light on its multifaceted functions and its associations with a spectrum of diseases. With a specific focus on neurological ailments, we delineate the intricate relationship that the omentum shares with other pathologies like stroke and we underly its contribution to serving as a therapeutic agent in neurological disorders. By deciphering the underlying mechanisms and emphasizing areas that demand further investigation. This review aims to spark renewed interest and pave the way for comprehensive studies exploring the greater omentum's potential in neurology and broader medicine overall. Given these diverse interactions that yet remain elusive, we must investigate and understand the nuanced relationship between the greater omentum and pathologies, especially its role in stroke's pathophysiology and therapeutic interventions so as to enhance patient care.
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Affiliation(s)
- Xiang Li
- Beijing Luhe Institute of Neuroscience, Capital Medical University, Beijing, China.
- Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
| | - Yuchuan Ding
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
| | - Yazeed W. Haddad
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
| | - Xiaokun Geng
- Beijing Luhe Institute of Neuroscience, Capital Medical University, Beijing, China.
- Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
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Mokhtari T, Uludag K. Role of NLRP3 Inflammasome in Post-Spinal-Cord-Injury Anxiety and Depression: Molecular Mechanisms and Therapeutic Implications. ACS Chem Neurosci 2024; 15:56-70. [PMID: 38109051 DOI: 10.1021/acschemneuro.3c00596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2023] Open
Abstract
The majority of research on the long-term effects of spinal cord injury (SCI) has primarily focused on neuropathic pain (NP), psychological issues, and sensorimotor impairments. Among SCI patients, mood disorders, such as anxiety and depression, have been extensively studied. It has been found that chronic stress and NP have negative consequences and reduce the quality of life for individuals living with SCI. Our review examined both human and experimental evidence to explore the connection between mood changes following SCI and inflammatory pathways, with a specific focus on NLRP3 inflammasome signaling. We observed increased proinflammatory factors in the blood, as well as in the brain and spinal cord tissues of SCI models. The NLRP3 inflammasome plays a crucial role in various diseases by controlling the release of proinflammatory molecules like interleukin 1β (IL-1β) and IL-18. Dysregulation of the NLRP3 inflammasome in key brain regions associated with pain processing, such as the prefrontal cortex and hippocampus, contributes to the development of mood disorders following SCI. In this review, we summarized recent research on the expression and regulation of components related to NLRP3 inflammasome signaling in mood disorders following SCI. Finally, we discussed potential therapeutic approaches that target the NLRP3 inflammasome and regulate proinflammatory cytokines as a way to treat mood disorders following SCI.
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Affiliation(s)
- Tahmineh Mokhtari
- Hubei Key Laboratory of Embryonic Stem Cell Research, Faculty of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, People's Republic of China
- Department of Histology and Embryology, Faculty of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, People's Republic of China
| | - Kadir Uludag
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, People's Republic of China
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Haeri Moghaddam N, Hashamdar S, Hamblin MR, Ramezani F. Effects of Electrospun Nanofibers on Motor Function Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis. World Neurosurg 2024; 181:96-106. [PMID: 37852475 DOI: 10.1016/j.wneu.2023.10.065] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/10/2023] [Accepted: 10/11/2023] [Indexed: 10/20/2023]
Abstract
Nanofibers made by electrospinning have been used as bridging materials in animal models to regenerate nerves after spinal cord injury (SCI). In this meta-analysis study, we investigated the effect of these nanofibers on the motor function of animals after SCI. An extensive search in databases was performed. After primary and secondary screening, data included functional behavior, expression of glial fibrillary acidic protein, neurofilament-200 (NF-200), and β-tubulin III were taken from the articles. The quality control of the articles, statistical analysis, and subgroup analysis were performed. The results from 14 articles and 16 separate experiments showed that electrospun nanofibers used alone could improve motor behavior and reduce glial injury after SCI.
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Affiliation(s)
- Niloofar Haeri Moghaddam
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Somayeh Hashamdar
- Physics Department, Amirkabir University of Technology, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Fatemeh Ramezani
- Physiology Research Centre, Iran University of Medical Sciences, Tehran, Iran.
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Lin FX, Pan QL, Gu HY, Zeng FJ, Lu ZJ. The Role of Resveratrol on Spinal Cord Injury: from Bench to Bedside. Mol Neurobiol 2024; 61:104-119. [PMID: 37584822 DOI: 10.1007/s12035-023-03558-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 08/05/2023] [Indexed: 08/17/2023]
Abstract
Spinal cord injury (SCI) is a severe and disabling injury of the central nervous system, with complex pathological mechanisms leading to sensory and motor dysfunction. Pathological processes, such as oxidative stress, inflammatory response, apoptosis, and glial scarring are important factors that aggravate SCI. Therefore, the inhibition of these pathological processes may contribute to the treatment of SCI. Currently, the pathogenesis of SCI remains under investigation as SCI treatment has not progressed considerably. Resveratrol, a natural polyphenol with anti-inflammatory and antioxidant properties, is considered a potential therapeutic drug for various diseases and plays a beneficial role in nerve damage. Preclinical studies have confirmed that signaling pathways are closely related to the pathological processes in SCI, and resveratrol is believed to exert therapeutic effects in SCI by activating the related signaling pathways. Based on current research on the pathways of resveratrol and its role in SCI, resveratrol may be a potentially effective treatment for SCI. This review summarizes the role of resveratrol in promoting the recovery of nerve function by regulating oxidative stress, inflammation, apoptosis, and glial scar formation in SCI through various mechanisms and pathways, as well as the deficiency of resveratrol in SCI research and the current and anticipated research trends of resveratrol. In addition, this review provides a background for further studies on the molecular mechanisms of SCI and the development of potential therapeutic agents. This information could also help clinicians understand the known mechanisms of action of resveratrol and provide better treatment options for patients with SCI.
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Affiliation(s)
- Fei-Xiang Lin
- Department of Spine Surgery, Ganzhou People's Hospital, 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China.
- Department of Spine Surgery, The Affiliated Ganzhou Hospital of Nanchang University, (Ganzhou Hospital-Nanfang Hospital, Southern Medical University), 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China.
| | - Qi-Lin Pan
- Department of Spine Surgery, Ganzhou People's Hospital, 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
- Department of Spine Surgery, The Affiliated Ganzhou Hospital of Nanchang University, (Ganzhou Hospital-Nanfang Hospital, Southern Medical University), 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
| | - Hou-Yun Gu
- Department of Spine Surgery, Ganzhou People's Hospital, 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
- Department of Spine Surgery, The Affiliated Ganzhou Hospital of Nanchang University, (Ganzhou Hospital-Nanfang Hospital, Southern Medical University), 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
| | - Fang-Jun Zeng
- Department of Spine Surgery, Ganzhou People's Hospital, 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
- Department of Spine Surgery, The Affiliated Ganzhou Hospital of Nanchang University, (Ganzhou Hospital-Nanfang Hospital, Southern Medical University), 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
| | - Zhi-Jun Lu
- Department of Spine Surgery, Ganzhou People's Hospital, 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
- Department of Spine Surgery, The Affiliated Ganzhou Hospital of Nanchang University, (Ganzhou Hospital-Nanfang Hospital, Southern Medical University), 16 Meiguan Avenue, Ganzhou, Jiangxi Province, 341000, People's Republic of China
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10
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André AD, Martins P. Exo Supportive Devices: Summary of Technical Aspects. Bioengineering (Basel) 2023; 10:1328. [PMID: 38002452 PMCID: PMC10669745 DOI: 10.3390/bioengineering10111328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/10/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Human societies have been trying to mitigate the suffering of individuals with physical impairments, with a special effort in the last century. In the 1950s, a new concept arose, finding similarities between animal exoskeletons, and with the goal of medically aiding human movement (for rehabilitation applications). There have been several studies on using exosuits with this purpose in mind. So, the current review offers a critical perspective and a detailed analysis of the steps and key decisions involved in the conception of an exoskeleton. Choices such as design aspects, base materials (structure), actuators (force and motion), energy sources (actuation), and control systems will be discussed, pointing out their advantages and disadvantages. Moreover, examples of exosuits (full-body, upper-body, and lower-body devices) will be presented and described, including their use cases and outcomes. The future of exoskeletons as possible assisted movement solutions will be discussed-pointing to the best options for rehabilitation.
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Affiliation(s)
- António Diogo André
- Associated Laboratory of Energy, Transports and Aeronautics (LAETA), Biomechanic and Health Unity (UBS), Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), 4200-465 Porto, Portugal;
- Faculty of Engineering, University of Porto (FEUP), 4200-465 Porto, Portugal
| | - Pedro Martins
- Associated Laboratory of Energy, Transports and Aeronautics (LAETA), Biomechanic and Health Unity (UBS), Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), 4200-465 Porto, Portugal;
- Aragon Institute for Engineering Research (i3A), Universidad de Zaragoza, 50018 Zaragoza, Spain
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11
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Lee SE, Greenough EK, Fonken LK, Gaudet AD. Spinal cord injury in mice amplifies anxiety: A novel light-heat conflict test exposes increased salience of anxiety over heat. Exp Neurol 2023; 364:114382. [PMID: 36924982 PMCID: PMC10874685 DOI: 10.1016/j.expneurol.2023.114382] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/24/2023] [Accepted: 03/11/2023] [Indexed: 03/17/2023]
Abstract
Spinal cord injury (SCI) predisposes individuals to anxiety and chronic pain. Anxiety- and pain-like behavior after SCI can be tested in rodents, yet commonly used tests assess one variable and may not replicate effects of SCI or sex differences seen in humans. Thus, novel preclinical tests should be optimized to better evaluate behaviors relating to anxiety and pain. Here, we use our newly developed conflict test - the Thermal Increments Dark-Light (TIDAL) test - to explore how SCI affects anxiety- vs. pain-like behavior, and whether sex affects post-SCI behavior. The TIDAL conflict test consists of two plates connected by a walkway; one plate remains illuminated and at an isothermic temperature, whereas the other plate is dark but is heated incrementally to aversive temperatures. A control mice thermal place preference test was also performed in which both plates are illuminated. Female and male mice received moderate T9 contusion SCI or remained uninjured. At 7 days post-operative (dpo), mice with SCI increased dark plate preference throughout the TIDAL conflict test compared to uninjured mice. SCI increased dark plate preference for both sexes, although female (vs. male) mice remained on the heated-dark plate to higher temperatures. Mice with SCI that repeated TIDAL at 7 and 21 dpo showed reduced preference for the dark-heated plate at 21 dpo. Overall, in female and male mice, SCI enhances the salience of anxiety (vs. heat sensitivity). The TIDAL conflict test meets a need for preclinical anxiety- and pain-related tests that recapitulate the human condition; thus, future rodent behavioral studies should incorporate TIDAL or other conflict tests to help understand and treat neurologic disorders.
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Affiliation(s)
- Sydney E Lee
- Department of Psychology, College of Liberal Arts, The University of Texas at Austin, 108 E. Dean Keeton St, Mail Stop A800, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
| | - Emily K Greenough
- Department of Psychology, College of Liberal Arts, The University of Texas at Austin, 108 E. Dean Keeton St, Mail Stop A800, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
| | - Laura K Fonken
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W. Dean Keeton St, Stop C0875 BME 3.510, Austin, TX 78712, USA.
| | - Andrew D Gaudet
- Department of Psychology, College of Liberal Arts, The University of Texas at Austin, 108 E. Dean Keeton St, Mail Stop A800, Austin, TX 78712, USA; Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
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12
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Han T, Song P, Wu Z, Liu Y, Ying W, Shen C. Inflammation Modifies miR-21 Expression Within Neuronal Extracellular Vesicles to Regulate Remyelination Following Spinal Cord Injury. Stem Cell Rev Rep 2023:10.1007/s12015-023-10560-y. [PMID: 37256514 PMCID: PMC10390616 DOI: 10.1007/s12015-023-10560-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2023] [Indexed: 06/01/2023]
Abstract
Cell‒cell communication following spinal cord injury (SCI) plays a key role in remyelination and neurological recovery. Although communication between neuron-neural stem cells (NSCs) affects remyelination, its precise mechanism remains unclear. The present study investigated the biological effects of extracellular vesicles (EVs) derived from neurons on the differentiation of NSCs and the remyelination of axons in a rat model for SCI. We found that that EVs derived from neurons promoted the differentiation of NSCs into oligodendrocytes and the remyelination of axons in SCI rats. However, neuron-derived EVs lost their biological effects after inflammatory stimulation of these neurons from which they originate. Further analysis demonstrated that the inflammatory stimulation on neurons upregulated miR-21 within EVs, which targeted SMAD 7 and upregulated the TGF-β/SMAD2 signaling pathway, resulting in an excess of astrocytic scar boundaries and in remyelination failure. Moreover, these effects could be abolished by miR-21 inhibitors/antagomirs. Considered together, these results indicate that inflammatory stimulation of neurons prevents remyelination following SCI via the upregulation of miR-21 expression within neuron-derived EVs, and this takes place through SMAD 7-mediated activation of the TGF-β/SMAD2 signaling pathway. Graphical Astract.
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Affiliation(s)
- Tianyu Han
- Department of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei City, Anhui Province, China
| | - Peiwen Song
- Department of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei City, Anhui Province, China
| | - Zuomeng Wu
- Department of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei City, Anhui Province, China
| | - Yunlei Liu
- Department of clinical laboratory, People's Hospital of Fuyang, Fuyang, China
| | - Wang Ying
- Department of Medical Imaging, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Cailiang Shen
- Department of Orthopedics (Spinal Surgery), The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei City, Anhui Province, China.
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13
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Baltin ME, Sabirova DE, Chernova ON, Baltina TV, Sachenkov OA. Morphofunctional Changes in the Spinal Cord of Rats after Contusion Injury with Local Delivery of Methylprednisolone in Combination with a Copolymer. Bull Exp Biol Med 2023; 174:810-815. [PMID: 37160795 DOI: 10.1007/s10517-023-05795-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Indexed: 05/11/2023]
Abstract
We studied the neuroprotective effect of local application of methylprednisolone in combination with a block copolymer after contusion spinal cord injury in rats. Histological analysis of the spinal cord showed that delivery of a complex of methylprednisolone with a block copolymer reduced the volume of white and gray matter lesions. An increase in the amplitude of the evoked response of the gastrocnemius muscle was observed during epidural stimulation of the spinal cord 6 h after the injury. The maximum amplitude of the muscle response was greater in the group with local delivery of the methylprednisolone complex with the polymer 72 h after the injury. The obtained results demonstrate the neuroprotective effect of the local administration of the complex and allow to make positive prognosis for the recovery of the sensorimotor functions in rats.
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Affiliation(s)
- M E Baltin
- Institute of Fundamental Medicine and Biology, Kazan (Volga region) Federal University, Kazan, Republic of Tatarstan, Russia
| | - D E Sabirova
- Institute of Fundamental Medicine and Biology, Kazan (Volga region) Federal University, Kazan, Republic of Tatarstan, Russia
| | | | - T V Baltina
- Institute of Fundamental Medicine and Biology, Kazan (Volga region) Federal University, Kazan, Republic of Tatarstan, Russia.
| | - O A Sachenkov
- N. I. Lobachevsky Institute of Mathematics and Mechanics, Kazan (Volga region) Federal University, Kazan, Republic of Tatarstan, Russia
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14
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Myatich A, Haque A, Sole C, Banik NL. Clemastine in remyelination and protection of neurons and skeletal muscle after spinal cord injury. Neural Regen Res 2023; 18:940-946. [PMID: 36254972 PMCID: PMC9827778 DOI: 10.4103/1673-5374.355749] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/20/2022] [Accepted: 08/16/2022] [Indexed: 11/05/2022] Open
Abstract
Spinal cord injuries affect nearly five to ten individuals per million every year. Spinal cord injury causes damage to the nerves, muscles, and the tissue surrounding the spinal cord. Depending on the severity, spinal injuries are linked to degeneration of axons and myelin, resulting in neuronal impairment and skeletal muscle weakness and atrophy. The protection of neurons and promotion of myelin regeneration during spinal cord injury is important for recovery of function following spinal cord injury. Current treatments have little to no effect on spinal cord injury and neurogenic muscle loss. Clemastine, an Food and Drug Administration-approved antihistamine drug, reduces inflammation, protects cells, promotes remyelination, and preserves myelin integrity. Recent clinical evidence suggests that clemastine can decrease the loss of axons after spinal cord injury, stimulating the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes that are capable of myelination. While clemastine can aid not only in the remyelination and preservation of myelin sheath integrity, it also protects neurons. However, its role in neurogenic muscle loss remains unclear. This review discusses the pathophysiology of spinal cord injury, and the role of clemastine in the protection of neurons, myelin, and axons as well as attenuation of skeletal muscle loss following spinal cord injury.
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Affiliation(s)
- Ali Myatich
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
- Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA
| | - Azizul Haque
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
- Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA
- Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA
| | - Christopher Sole
- Department of Health and Human Performance, The Citadel, Charleston, SC, USA
| | - Naren L. Banik
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
- Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA
- Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA
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15
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de Sire A, Moggio L, Marotta N, Curci C, Lippi L, Invernizzi M, Mezian K, Ammendolia A. Impact of rehabilitation on volumetric muscle loss in subjects with traumatic spinal cord injury: A systematic review. NeuroRehabilitation 2023; 52:365-386. [PMID: 36806523 DOI: 10.3233/nre-220277] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
Abstract
BACKGROUND Spinal cord injury (SCI) leads to spinal nerve fiber tract damage resulting in functional impairments. Volumetric muscle loss (VML), a skeletal muscle volume abnormal reduction, is represented by atrophy below the injury level. The strategies for VML management included personalized approaches, and no definite indications are available. OBJECTIVE To identify the rehabilitation effects of VML in subjects with SCI (humans and animals). METHODS PubMed, Scopus, and Web of Science databases were systematically searched to identify longitudinal observational studies with individuals affected by traumatic SCI as participants; rehabilitation treatment as intervention; no control, sham treatment, and electrical stimulation programs as control; total lean body and lower limb lean mass, cross-sectional area, functional gait recovery, muscle thickness, and ultrasound intensity, as outcome. RESULTS Twenty-four longitudinal observational studies were included, evaluating different rehabilitation approaches' effects on the VML reduction in subjects affected by SCI. The data showed that electrical stimulation and treadmill training are effective in reducing the VML in this population. CONCLUSION This systematic review underlines the need to treat subjects with traumatic SCI (humans and animals) with different rehabilitation approaches to prevent VML in the subacute and chronic phases. Further clinical observations are needed to overcome the bias and to define the intervention's timing and modalities.
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Affiliation(s)
- Alessandro de Sire
- Department of Medical and Surgical Sciences, Physical Medicine and Rehabilitation Unit, University of CatanzaroMagna Graecia, Catanzaro, Italy.,Department of Rehabilitation and Sports Medicine, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
| | - Lucrezia Moggio
- Department of Medical and Surgical Sciences, Physical Medicine and Rehabilitation Unit, University of CatanzaroMagna Graecia, Catanzaro, Italy.,Rehabilitation Unit, Ospedale degliInfermi, Biella, Italy
| | - Nicola Marotta
- Department of Medical and Surgical Sciences, Physical Medicine and Rehabilitation Unit, University of CatanzaroMagna Graecia, Catanzaro, Italy
| | - Claudio Curci
- Department of Neurosciences, Physical Medicine and Rehabilitation Unit, ASST CarloPoma, Mantova, Italy
| | - Lorenzo Lippi
- Department of Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy.,Translational Medicine, DipartimentoAttività Integrate Ricerca e Innovazione (DAIRI), AziendaOspedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | - Marco Invernizzi
- Department of Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy.,Translational Medicine, DipartimentoAttività Integrate Ricerca e Innovazione (DAIRI), AziendaOspedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
| | - Kamal Mezian
- Department of Rehabilitation Medicine, First Faculty of Medicine, Charles University and General UniversityHospital in Prague, Prague, Czech Republic
| | - Antonio Ammendolia
- Department of Medical and Surgical Sciences, Physical Medicine and Rehabilitation Unit, University of CatanzaroMagna Graecia, Catanzaro, Italy
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16
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Khaing ZZ, Chen JY, Safarians G, Ezubeik S, Pedroncelli N, Duquette RD, Prasse T, Seidlits SK. Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury. Int J Mol Sci 2023; 24:3824. [PMID: 36835233 PMCID: PMC9960771 DOI: 10.3390/ijms24043824] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023] Open
Abstract
Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction in quality of life for patients. Currently, no therapies are available that can repair spinal cord tissue. After the primary SCI, an acute inflammatory response induces further tissue damage in a process known as secondary injury. Targeting secondary injury to prevent additional tissue damage during the acute and subacute phases of SCI represents a promising strategy to improve patient outcomes. Here, we review clinical trials of neuroprotective therapeutics expected to mitigate secondary injury, focusing primarily on those in the last decade. The strategies discussed are broadly categorized as acute-phase procedural/surgical interventions, systemically delivered pharmacological agents, and cell-based therapies. In addition, we summarize the potential for combinatorial therapies and considerations.
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Affiliation(s)
- Zin Z. Khaing
- Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA
| | - Jessica Y. Chen
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Gevick Safarians
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Sohib Ezubeik
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Nicolas Pedroncelli
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
| | - Rebecca D. Duquette
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
| | - Tobias Prasse
- Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA
- Department of Orthopedics and Trauma Surgery, University of Cologne, 50931 Cologne, Germany
| | - Stephanie K. Seidlits
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
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17
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The aOECs Facilitate the Neuronal Differentiation of Neural Stem Cells in the Inflammatory Microenvironment Through Up-Regulation of Bioactive Factors and Activation of Wnt3/β-Catenin Pathway. Mol Neurobiol 2023; 60:789-806. [PMID: 36371572 DOI: 10.1007/s12035-022-03113-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 10/29/2022] [Indexed: 11/13/2022]
Abstract
The therapeutic application of neural stem cells (NSCs) in the central nerve system (CNS) injury is a promising strategy for combating irreversible neuronal loss. However, a variety of obvious inflammatory responses following nerve injury rapidly create an unfavorable microenvironment for survival and neuronal differentiation of NSCs in lesion area, limiting the efficacy of NSC-based therapy for CNS injury. It remained unknown how to effectively increase the neuronal differentiation efficiency of NSCs through transplantation. Here, we demonstrated that curcumin (CCM)-activated olfactory ensheathing cells (aOECs) effectively promoted neuronal differentiation of NSCs in the activated microglial inflammatory condition, and co-transplantation of aOECs and NSCs improved neurological recovery of rats after spinal cord injury (SCI), as evidenced by higher expression levels of neuronal markers and lower expression levels of glial markers in the differentiated cells, greater number of Tuj-1-positive cells as well as higher Basso, Beattie, and Bresnahan (BBB) locomotor scale, compared to the corresponding controls. Pathologically, hematoxylin and eosin (HE) staining and immunostaining also showed that aOECs remarkably enhanced the in vivo neuronal differentiation of NSCs and migration, and nerve repair. Further analysis revealed that the underlying mechanisms of aOECs potentiating the neuronal conversion of NSCs under inflammatory environment were tightly associated with up-regulation of anti-inflammatory cytokines and neurotrophic factors in OECs, and importantly, the activation of Wnt3/β-catenin pathway was likely involved in the mechanisms underlying the observed cellular events. Therefore, this study provides a promising strategy for SCI repair by co-transplantation of aOECs and NSCs.
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18
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Stepanova OV, Fursa GA, Andretsova SS, Shishkina VS, Voronova AD, Chadin AV, Karsuntseva EK, Reshetov IV, Chekhonin VP. Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries. World J Clin Cases 2023; 11:322-331. [PMID: 36686356 PMCID: PMC9850961 DOI: 10.12998/wjcc.v11.i2.322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/28/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023] Open
Abstract
The review focuses on the most important areas of cell therapy for spinal cord injuries. Olfactory mucosa cells are promising for transplantation. Obtaining these cells is safe for patients. The use of olfactory mucosa cells is effective in restoring motor function due to the remyelination and regeneration of axons after spinal cord injuries. These cells express neurotrophic factors that play an important role in the functional recovery of nerve tissue after spinal cord injuries. In addition, it is possible to increase the content of neurotrophic factors, at the site of injury, exogenously by the direct injection of neurotrophic factors or their delivery using gene therapy. The advantages of olfactory mucosa cells, in combination with neurotrophic factors, open up wide possibilities for their application in three-dimensional and four-dimensional bioprinting technology treating spinal cord injuries.
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Affiliation(s)
- Olga Vladislavovna Stepanova
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
- Department of Neurohumoral and Immunological Research, National Medical Research Center of Cardiology, Moscow 121552, Russia
| | - Grigorii Andreevich Fursa
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | - Svetlana Sergeevna Andretsova
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
- Department of Biology, Moscow State University, Moscow 119991, Russia
| | - Valentina Sergeevna Shishkina
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | - Anastasia Denisovna Voronova
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | - Andrey Viktorovich Chadin
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
| | | | | | - Vladimir Pavlovich Chekhonin
- Department of Basic and Applied Neurobiology, V.P. Serbsky National Medical Research Center for Psychiatry and Narcology, Moscow 119034, Russia
- Department of Medical Nanobiotechnologу, N.I. Pirogov Russian National Research Medical University, Moscow 117997, Russia
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19
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Lee BJ, Jeong JH. Early Decompression in Acute Spinal Cord Injury : Review and Update. J Korean Neurosurg Soc 2023; 66:6-11. [PMID: 36274255 PMCID: PMC9837486 DOI: 10.3340/jkns.2022.0107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/25/2022] [Accepted: 07/01/2022] [Indexed: 01/25/2023] Open
Abstract
Spinal cord injury (SCI) has a significant negative effect on the quality of life due to permanent neurologic damage and economic burden by continuous treatment and rehabilitation. However, determining the correct approach to ensure optimal clinical outcomes can be challenging and remains highly controversial. In particular, with the introduction of the concept of early decompression in brain pathology, the discussion of the timing of decompression in SCI has emerged. In addition to that, the concept of "time is spine" has been added recently, and the mortality and complications caused by SCI have been reduced by providing timely and professional treatment to patients. However, there are many difficulties in establishing international clinical guidelines for the timing of early decompression in SCI because policies for each country and medical institution differ according to the circumstances of medical infrastructure and economic conditions in the surgical treatment of SCI. Therefore, we aim to provide a current review of timing of early decompression in patient with SCI.
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Affiliation(s)
- Byung-Jou Lee
- Department of Neurosurgery and Neuroscience & Radiosurgery Hybrid Research Center, Inje University Ilsan Paik Hospital, College of Medicine, Inje University, Goyang, Korea
| | - Je Hoon Jeong
- Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
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20
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Zhou L, Yan K, Xing S, Cheng J. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6. Open Med (Wars) 2023; 18:20230680. [PMID: 37069938 PMCID: PMC10105551 DOI: 10.1515/med-2023-0680] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 02/05/2023] [Accepted: 02/23/2023] [Indexed: 04/19/2023] Open
Abstract
Since tectorigenin has been reported to possess anti-inflammation, redox balance restoration, and anti-apoptosis properties, we determine to unravel whether tectorigenin has potential in alleviating spinal cord injury (SCI). Herein, PC12 cells were induced by lipopolysaccharide (LPS) to establish in vitro SCI models. The cell viability and apoptosis were detected through cell counting kit-8 and flow cytometry assays. The caspase-3/8/9 content was measured by colorimetric method. Western blot was conducted to quantify the expressions of cleaved caspse-3/8/9, IGFBP6, TLR4, IκBα, p-IκBα, RELA proto-oncogene, p65, and p-p65. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction were carried out to quantitate expressions of IGFBP6, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). SwissTargetPrediction and GSE21497 database were utilized to predict the potential therapeutic targets of tectorigenin. Comparison of IGFBP6 expression in SCI tissues and normal tissues was analyzed by GEO2R. Our study found that LPS induced the declined cell viability, elevated cell apoptosis, upregulation of caspase-3/8/9, cleaved caspase-3/8/9, IL-1β, IL-6, TNF-α, IGFBP6, and TLR4, and the activation of IκBα and p65 in PC12 cells. Tectorigenin reversed the above effects of LPS. IGFBP6 was predicted to be the potential therapeutic target of tectorigenin and was overexpressed in SCI tissues. Notably, IGFBP6 overexpression offset the effects of tectorigenin on PC12 cells. In conclusion, tectorigenin could alleviate the LPS-induced apoptosis, inflammation, and activation of NF-κB signaling in SCI cell models via inhibiting IGFBP6.
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Affiliation(s)
- Liqiang Zhou
- Department of Orthopedics, Chengdu Fifth People’s Hospital, Chengdu, Sichuan Province, 611130, China
| | - Kui Yan
- Department of Orthopedics, Chengdu Fifth People’s Hospital, Chengdu, Sichuan Province, 611130, China
| | - Shuxing Xing
- Department of Orthopedics, Chengdu Fifth People’s Hospital, No. 33 Mashi Street, Wenjiang
District, Chengdu, Sichuan Province, 611130, China
| | - Jun Cheng
- Department of Orthopedics, Chengdu Fifth People’s Hospital, Chengdu, Sichuan Province, 611130, China
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21
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Silvestro S, Mazzon E. Nrf2 Activation: Involvement in Central Nervous System Traumatic Injuries. A Promising Therapeutic Target of Natural Compounds. Int J Mol Sci 2022; 24:199. [PMID: 36613649 PMCID: PMC9820431 DOI: 10.3390/ijms24010199] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/15/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
Central nervous system (CNS) trauma, such as traumatic brain injury (TBI) and spinal cord injury (SCI), represents an increasingly important health burden in view of the preventability of most injuries and the complex and expensive medical care that they necessitate. These injuries are characterized by different signs of neurodegeneration, such as oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. Cumulative evidence suggests that the transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial defensive role in regulating the antioxidant response. It has been demonstrated that several natural compounds are able to activate Nrf2, mediating its antioxidant response. Some of these compounds have been tested in experimental models of SCI and TBI, showing different neuroprotective properties. In this review, an overview of the preclinical studies that highlight the positive effects of natural bioactive compounds in SCI and TBI experimental models through the activation of the Nrf2 pathway has been provided. Interestingly, several natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response against CNS trauma. Therefore, some of these compounds could represent promising therapeutic strategies for these pathological conditions.
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Affiliation(s)
| | - Emanuela Mazzon
- IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
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22
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Bak AB, Moghaddamjou A, Malvea A, Fehlings MG. Impact of Mechanism of Injury on Long-term Neurological Outcomes of Cervical Sensorimotor Complete Acute Traumatic Spinal Cord Injury. Neurospine 2022; 19:1049-1056. [PMID: 36597641 PMCID: PMC9816602 DOI: 10.14245/ns.2244518.259] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/14/2022] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE Mechanism of injury is a largely understudied descriptor of acute traumatic spinal cord injury (tSCI). This study sought to compare the impact of high-energy and low-energy mechanisms of injury in neurological outcomes of cervical sensorimotor complete tSCI. METHODS Patients with tSCI were identified in 4 prospective, multicenter clinical trials and registries. American Spinal Injury Association Impairment Scale (AIS) grade was assessed ≤ 72 hours postinjury and followed up between 12 to 52 weeks. Patients were included if they had a cervical and sensorimotor complete (AIS-A) injury at baseline. Study outcomes were change in AIS grade and lower extremity motor, upper extremity motor, and total motor scores. Propensity score matching between high-energy mechanisms of injury (HEMI; e.g. , motor vehicle collisions) and low-energy mechanisms of injury (LEMI; e.g. , falls) groups was performed. Adjusted groups were compared with paired t-tests and McNemar test. RESULTS Of 667 patients eligible for inclusion, 523 experienced HEMI (78.4%). HEMI patients were younger, had lower body mass index, more associated fractures or dislocations, and lower baseline lower extremity motor scores. After propensity score matching of these baseline variables, 118 pairs were matched. HEMI patients had a significantly worse motor recovery from baseline to follow-up based on their diminished change in upper extremity motor scores and total motor scores. CONCLUSION Cervical sensorimotor complete tSCIs from HEMI were associated with significantly lower motor recovery compared to LEMI patients. Our findings suggest that mechanism of injury should be considered in modelling prognosis and in understanding the heterogeneity of outcomes after acute tSCI.
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Affiliation(s)
- Alex B. Bak
- Division of Neurosurgery, Department of Surgery, University of Toronto Faculty of Medicine, Toronto, ON, Canada,Krembil Research Institute, University Health Network, Toronto, ON, Canada,Spine Program, University of Toronto Faculty of Medicine, Toronto, ON, Canada
| | - Ali Moghaddamjou
- Division of Neurosurgery, Department of Surgery, University of Toronto Faculty of Medicine, Toronto, ON, Canada,Krembil Research Institute, University Health Network, Toronto, ON, Canada,Spine Program, University of Toronto Faculty of Medicine, Toronto, ON, Canada
| | - Anahita Malvea
- Division of Neurosurgery, Department of Surgery, University of Toronto Faculty of Medicine, Toronto, ON, Canada
| | - Michael G. Fehlings
- Division of Neurosurgery, Department of Surgery, University of Toronto Faculty of Medicine, Toronto, ON, Canada,Krembil Research Institute, University Health Network, Toronto, ON, Canada,Spine Program, University of Toronto Faculty of Medicine, Toronto, ON, Canada,Corresponding Author Michael G. Fehlings Toronto Western Hospital, 399 Bathurst Street, Suite 4WW-449, Toronto, ON, Canada
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Roolfs L, Hubertus V, Spinnen J, Shopperly LK, Fehlings MG, Vajkoczy P. Therapeutic Approaches Targeting Vascular Repair After Experimental Spinal Cord Injury: A Systematic Review of the Literature. Neurospine 2022; 19:961-975. [PMID: 36597633 PMCID: PMC9816606 DOI: 10.14245/ns.2244624.312] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 09/16/2022] [Indexed: 12/27/2022] Open
Abstract
Traumatic spinal cord injury (SCI) disrupts the spinal cord vasculature resulting in ischemia, amplification of the secondary injury cascade and exacerbation of neural tissue loss. Restoring functional integrity of the microvasculature to prevent neural loss and to promote neural repair is an important challenge and opportunity in SCI research. Herein, we summarize the course of vascular injury and repair following SCI and give a comprehensive overview of current experimental therapeutic approaches targeting spinal cord microvasculature to diminish ischemia and thereby facilitate neural repair and regeneration. A systematic review of the published literature on therapeutic approaches to promote vascular repair after experimental SCI was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. The MEDLINE databases PubMed, Embase, and OVID MEDLINE were searched using the keywords "spinal cord injury," "angiogenesis," "angiogenesis inducing agents," "tissue engineering," and "rodent subjects." A total of 111 studies were identified through the search. Five main therapeutic approaches to diminish hypoxia-ischemia and promote vascular repair were identified as (1) the application of angiogenic factors, (2) genetic engineering, (3) physical stimulation, (4) cell transplantation, and (5) biomaterials carrying various factor delivery. There are different therapeutic approaches with the potential to diminish hypoxia-ischemia and promote vascular repair after experimental SCI. Of note, combinatorial approaches using implanted biomaterials and angiogenic factor delivery appear promising for clinical translation.
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Affiliation(s)
- Laurens Roolfs
- Department of Neurosurgery, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
| | - Vanessa Hubertus
- Department of Neurosurgery, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
| | - Jacob Spinnen
- Tissue Engineering Laboratory, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
| | - Lennard K. Shopperly
- Tissue Engineering Laboratory, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
| | - Michael G. Fehlings
- Division of Neurosurgery and Krembil Neuroscience Centre, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Canada
| | - Peter Vajkoczy
- Department of Neurosurgery, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany,Corresponding Author Peter Vajkoczy Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany
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24
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Li Q, Guo Y, Xu C, Sun J, Zeng F, Lin S, Yuan Y. Therapy of spinal cord injury by folic acid polyethylene glycol amine-modified zeolitic imidazole framework-8 nanoparticles targeted activated M/Ms. Front Bioeng Biotechnol 2022; 10:959324. [PMID: 36185443 PMCID: PMC9519986 DOI: 10.3389/fbioe.2022.959324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Excessively activated microglia/macrophages (M/Ms) re-establish the proinflammatory microenvironment that exacerbates motor and/or sensory dysfunction after spinal cord injury (SCI). Thus, proinflammatory M/Ms-suppressed treatments may be effective strategies for SCI. However, the utilization of anti-inflammatory drugs for clinical approaches and biomedical research has side effects, such as nephrotoxicity and hepatotoxicity. In this study, we fabricated folic acid-polyethylene glycol (FA-PEG) amine-modified zeolitic imidazole framework-8 (ZIF-8) nanoparticles (FA-PEG/ZIF-8) and found that it effectively restored function in vivo. FA-PEG/ZIF-8 treatment significantly eliminated proinflammatory M/Ms without targeting other nerve cells and downregulated inflammation in the injured lesion. Furthermore, FA-PEG/ZIF-8 caused little toxicity in SCI mice compared to normal mice. These results suggest that FA-PEG/ZIF-8 has the potential to help recover from early-stage SCI by suppressing proinflammatory M/Ms.
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Affiliation(s)
- Qi Li
- Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Yue Guo
- Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Chang Xu
- Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Jiachen Sun
- Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Fanzhuo Zeng
- Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Sen Lin
- Key Laboratory of Medical Tissue Engineering, Jinzhou Medical University, Jinzhou, China
- *Correspondence: Sen Lin, ; Yajiang Yuan,
| | - Yajiang Yuan
- Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
- Key Laboratory of Medical Tissue Engineering, Jinzhou Medical University, Jinzhou, China
- *Correspondence: Sen Lin, ; Yajiang Yuan,
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25
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Islam F, Bepary S, Nafady MH, Islam MR, Emran TB, Sultana S, Huq MA, Mitra S, Chopra H, Sharma R, Sweilam SH, Khandaker MU, Idris AM. Polyphenols Targeting Oxidative Stress in Spinal Cord Injury: Current Status and Future Vision. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8741787. [PMID: 36046682 PMCID: PMC9423984 DOI: 10.1155/2022/8741787] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/03/2022] [Accepted: 08/03/2022] [Indexed: 02/07/2023]
Abstract
A spinal cord injury (SCI) occurs when the spinal cord is deteriorated or traumatized, leading to motor and sensory functions lost even totally or partially. An imbalance within the generation of reactive oxygen species and antioxidant defense levels results in oxidative stress (OS) and neuroinflammation. After SCI, OS and occurring pathways of inflammations are significant strenuous drivers of cross-linked dysregulated pathways. It emphasizes the significance of multitarget therapy in combating SCI consequences. Polyphenols, which are secondary metabolites originating from plants, have the promise to be used as alternative therapeutic agents to treat SCI. Secondary metabolites have activity on neuroinflammatory, neuronal OS, and extrinsic axonal dysregulated pathways during the early stages of SCI. Experimental and clinical investigations have noted the possible importance of phenolic compounds as important phytochemicals in moderating upstream dysregulated OS/inflammatory signaling mediators and axonal regeneration's extrinsic pathways after the SCI probable significance of phenolic compounds as important phytochemicals in mediating upstream dysregulated OS/inflammatory signaling mediators. Furthermore, combining polyphenols could be a way to lessen the effects of SCI.
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Affiliation(s)
- Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Sristy Bepary
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Mohamed H. Nafady
- Faculty of Applied Health Science Technology, Misr University for Science and Technology, Giza, Egypt
| | - Md. Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
| | - Sharifa Sultana
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
| | - Md. Amdadul Huq
- Department of Food and Nutrition, Chung Ang University, Anseong-Si, Gyeonggi-Do 17546, Republic of Korea
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Rohit Sharma
- Department of Rasashastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Sherouk Hussein Sweilam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Cairo-Suez Road, Badr City 11829, Egypt
| | - Mayeen Uddin Khandaker
- Centre for Applied Physics and Radiation Technologies, School of Engineering and Technology, Sunway University, 47500 Bandar Sunway, Selangor, Malaysia
| | - Abubakr M. Idris
- Department of Chemistry, College of Science, King Khalid University, Abha 62529, Saudi Arabia
- Research Center for Advanced Materials Science (RCAMS), King Khalid University, Abha 62529, Saudi Arabia
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26
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Munteanu C, Rotariu M, Turnea M, Ionescu AM, Popescu C, Spinu A, Ionescu EV, Oprea C, Țucmeanu RE, Tătăranu LG, Silișteanu SC, Onose G. Main Cations and Cellular Biology of Traumatic Spinal Cord Injury. Cells 2022; 11:2503. [PMID: 36010579 PMCID: PMC9406880 DOI: 10.3390/cells11162503] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/06/2022] [Accepted: 08/09/2022] [Indexed: 02/08/2023] Open
Abstract
Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the community. Despite considerable medical advances, there is still a lack of options for the effective treatment of these patients. The major complexity and significant disabling potential of the pathophysiology that spinal cord trauma triggers are the main factors that have led to incremental scientific research on this topic, including trying to describe the molecular and cellular mechanisms that regulate spinal cord repair and regeneration. Scientists have identified various practical approaches to promote cell growth and survival, remyelination, and neuroplasticity in this part of the central nervous system. This review focuses on specific detailed aspects of the involvement of cations in the cell biology of such pathology and on the possibility of repairing damaged spinal cord tissue. In this context, the cellular biology of sodium, potassium, lithium, calcium, and magnesium is essential for understanding the related pathophysiology and also the possibilities to counteract the harmful effects of traumatic events. Lithium, sodium, potassium-monovalent cations-and calcium and magnesium-bivalent cations-can influence many protein-protein interactions, gene transcription, ion channel functions, cellular energy processes-phosphorylation, oxidation-inflammation, etc. For data systematization and synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, trying to make, as far as possible, some order in seeing the "big forest" instead of "trees". Although we would have expected a large number of articles to address the topic, we were still surprised to find only 51 unique articles after removing duplicates from the 207 articles initially identified. Our article integrates data on many biochemical processes influenced by cations at the molecular level to understand the real possibilities of therapeutic intervention-which must maintain a very narrow balance in cell ion concentrations. Multimolecular, multi-cellular: neuronal cells, glial cells, non-neuronal cells, but also multi-ionic interactions play an important role in the balance between neuro-degenerative pathophysiological processes and the development of effective neuroprotective strategies. This article emphasizes the need for studying cation dynamics as an important future direction.
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Affiliation(s)
- Constantin Munteanu
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700454 Iași, Romania
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania
| | - Mariana Rotariu
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700454 Iași, Romania
| | - Marius Turnea
- Faculty of Medical Bioengineering, University of Medicine and Pharmacy “Grigore T. Popa” Iași, 700454 Iași, Romania
| | - Anca Mirela Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania
| | - Cristina Popescu
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania
| | - Aura Spinu
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania
| | - Elena Valentina Ionescu
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | - Carmen Oprea
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | - Roxana Elena Țucmeanu
- Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania
- Balneal and Rehabilitation Sanatorium of Techirghiol, 906100 Techirghiol, Romania
| | - Ligia Gabriela Tătăranu
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania
| | - Sînziana Calina Silișteanu
- Faculty of Medicine and Biological Sciences, “Stefan cel Mare” University of Suceava, 720229 Suceava, Romania
| | - Gelu Onose
- Neuromuscular Rehabilitation Division, Teaching Emergency Hospital “Bagdasar-Arseni”, 041915 Bucharest, Romania
- Faculty of Medicine, University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania
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MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury. Cells 2022; 11:cells11142177. [PMID: 35883621 PMCID: PMC9318426 DOI: 10.3390/cells11142177] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/08/2022] [Accepted: 07/10/2022] [Indexed: 12/10/2022] Open
Abstract
Spinal cord injury (SCI) represents a devastating injury to the central nervous system (CNS) that is responsible for impaired mobility and sensory function in SCI patients. The hallmarks of SCI include neuroinflammation, axonal degeneration, neuronal loss, and reactive gliosis. Current strategies, including stem cell transplantation, have not led to successful clinical therapy. MiRNAs are crucial for the differentiation of neural cell types during CNS development, as well as for pathological processes after neural injury including SCI. This makes them ideal candidates for therapy in this condition. Indeed, several studies have demonstrated the involvement of miRNAs that are expressed differently in CNS injury. In this context, the purpose of the review is to provide an overview of the pre-clinical evidence evaluating the use of miRNA therapy in SCI. Specifically, we have focused our attention on miRNAs that are widely associated with neuronal and axon regeneration. “MiRNA replacement therapy” aims to transfer miRNAs to diseased cells and improve targeting efficacy in the cells, and this new therapeutic tool could provide a promising technique to promote SCI repair and reduce functional deficits.
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28
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Jiang Y, Guo J, Tang X, Wang X, Hao D, Yang H. The Immunological Roles of Olfactory Ensheathing Cells in the Treatment of Spinal Cord Injury. Front Immunol 2022; 13:881162. [PMID: 35669779 PMCID: PMC9163387 DOI: 10.3389/fimmu.2022.881162] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 04/22/2022] [Indexed: 01/16/2023] Open
Abstract
Spinal cord injury (SCI) is a devastating type of neurological disorder of the central nervous system (CNS) with high mortality and disability. The pathological processes of SCI can usually be described as two stages, namely, primary and acute secondary injuries. Secondary injury produces more significant exacerbations of the initial injury. Among all the mechanisms of secondary damage, infection and inflammatory responses, as the principle culprits in initiating the second phase of SCI, can greatly contribute to the severity of SCI and numerous sequelae after SCI. Therefore, effectively antagonizing pro-inflammatory responses may be a promising treatment strategy to facilitate functional recovery after SCI. Olfactory ensheathing cells (OECs), a unique type of glial cells, have increasingly become potential candidates for cell-based therapy in the injured CNS. Strikingly, there is growing evidence that the mechanisms underlying the anti-inflammatory role of OECs are associated with the immune properties and secretory functions of these cells responsible for anti-neuroinflammation and immunoregulatory effects, leading to maintenance of the internal microenvironment. Accordingly, a more profound understanding of the mechanism of OEC immunological functions in the treatment of SCI would be beneficial to improve the therapeutic clinical applications of OECs for SCI. In this review, we mainly summarize recent research on the cellular and molecular immune attributes of OECs. The unique biological functions of these cells in promoting neural regeneration are discussed in relation of the development of novel therapies for CNS injury.
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Affiliation(s)
- Yizhen Jiang
- Translational Medicine Center, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Jianbin Guo
- Department of Joint Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Xiangwen Tang
- Translational Medicine Center, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, China
- Basic Medical School Academy, Shaanxi University of Traditional Chinese Medicine, Xianyang, China
| | - Xiaohui Wang
- Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Dingjun Hao
- Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Hao Yang
- Translational Medicine Center, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, China
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29
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Feng Y, Li Y, Shen PP, Wang B. Gene-Modified Stem Cells for Spinal Cord Injury: a Promising Better Alternative Therapy. Stem Cell Rev Rep 2022; 18:2662-2682. [PMID: 35587330 DOI: 10.1007/s12015-022-10387-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2022] [Indexed: 12/18/2022]
Abstract
Stem cell therapy holds great promise for the treatment of spinal cord injury (SCI), which can reverse neurodegeneration and promote tissue regeneration via its pluripotency and ability to secrete neurotrophic factors. Although various stem cell-based approaches have shown certain therapeutic effects when applied to the treatment of SCI, their clinical efficacies have been disappointing. Thus, it is an urgent need to further enhance the neurological benefits of stem cells through bioengineering strategies including genetic engineering. In this review, we summarize the progress of stem cell therapy for SCI and the prospect of genetically modified stem cells, focusing on the genome editing tools and functional molecules involved in SCI repair, trying to provide a deeper understanding of genetically modified stem cell therapy and more applicable clinical strategies for SCI repair.
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Affiliation(s)
- Yirui Feng
- Clinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, School of Life Science, Nanjing University, Nanjing, Jiangsu Province, China
| | - Yu Li
- Clinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, School of Life Science, Nanjing University, Nanjing, Jiangsu Province, China
| | - Ping-Ping Shen
- State Key Laboratory of Pharmaceutical Biotechnology and the Comprehensive Cancer Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, School of Life Science, Nanjing University, Nanjing, Jiangsu Province, China.
| | - Bin Wang
- Clinical Stem Cell Center, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
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Hypothermia Therapy for Traumatic Spinal Cord Injury: An Updated Review. J Clin Med 2022; 11:jcm11061585. [PMID: 35329911 PMCID: PMC8949322 DOI: 10.3390/jcm11061585] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/07/2022] [Accepted: 03/10/2022] [Indexed: 11/16/2022] Open
Abstract
Although hypothermia has shown to protect against ischemic and traumatic neuronal death, its potential role in neurologic recovery following traumatic spinal cord injury (TSCI) remains incompletely understood. Herein, we systematically review the safety and efficacy of hypothermia therapy for TSCI. The English medical literature was reviewed using PRISMA guidelines to identify preclinical and clinical studies examining the safety and efficacy of hypothermia following TSCI. Fifty-seven articles met full-text review criteria, of which twenty-eight were included. The main outcomes of interest were neurological recovery and postoperative complications. Among the 24 preclinical studies, both systemic and local hypothermia significantly improved neurologic recovery. In aggregate, the 4 clinical studies enrolled 60 patients for treatment, with 35 receiving systemic hypothermia and 25 local hypothermia. The most frequent complications were respiratory in nature. No patients suffered neurologic deterioration because of hypothermia treatment. Rates of American Spinal Injury Association (AIS) grade conversion after systemic hypothermia (35.5%) were higher when compared to multiple SCI database control studies (26.1%). However, no statistical conclusions could be drawn regarding the efficacy of hypothermia in humans. These limited clinical trials show promise and suggest therapeutic hypothermia to be safe in TSCI patients, though its effect on neurological recovery remains unclear. The preclinical literature supports the efficacy of hypothermia after TSCI. Further clinical trials are warranted to conclusively determine the effects of hypothermia on neurological recovery as well as the ideal means of administration necessary for achieving efficacy in TSCI.
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31
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Yuan H, Fang CL, Deng YP, Huang J, Niu RZ, Chen JL, Chen TB, Zhu ZQ, Chen L, Xiong LL, Wang TH. A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway. Neurochirurgie 2022; 68:188-195. [PMID: 34543615 DOI: 10.1016/j.neuchi.2021.09.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 08/21/2021] [Accepted: 09/04/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. METHODS OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. RESULTS IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. CONCLUSIONS A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.
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Affiliation(s)
- H Yuan
- Institute of Neuroscience, Kunming Medical University, Kunming 650031, Yunnan, China; Department of Spine Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China
| | - C-L Fang
- Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; Department of Anesthesiology, National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Y-P Deng
- Department of Anesthesiology, National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - J Huang
- Institute of Neuroscience, Kunming Medical University, Kunming 650031, Yunnan, China
| | - R-Z Niu
- Laboratory Animal Department, Kunming Medical University, Kunming 650031, Yunnan, China
| | - J-L Chen
- Laboratory Animal Department, Kunming Medical University, Kunming 650031, Yunnan, China
| | - T-B Chen
- Laboratory Animal Department, Kunming Medical University, Kunming 650031, Yunnan, China
| | - Z-Q Zhu
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China
| | - L Chen
- Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - L-L Xiong
- Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China
| | - T-H Wang
- Institute of Neuroscience, Kunming Medical University, Kunming 650031, Yunnan, China; Laboratory Animal Department, Kunming Medical University, Kunming 650031, Yunnan, China; Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
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Khanna P, Garg H, Kumar S, Hemachandran N, Goel P, Kandasamy D, Bajpai M. Dura-to-spinal cord distance at different vertebral levels in Indian children: A retrospective computerized tomography scan-based study. Anesth Essays Res 2022; 16:138-142. [PMID: 36249143 PMCID: PMC9558667 DOI: 10.4103/aer.aer_26_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 04/28/2022] [Accepted: 05/20/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Neuraxial techniques provide good postoperative analgesia for painful procedures in the pediatric population. However, any injury to the spinal cord can lead to irreversible long-term effects. Aims: We aimed to evaluate dura-to-cord (DTC) distance from computerized tomography (CT) images of thoracolumbar spine in pediatric age group (1–16 years) at T8–9, T9–10, and L1–2 interspaces to identify the safe space for epidural insertion in Asian children. Settings and Design: It was a retrospective study including 141 children aged 1–16 years who underwent routine CT scan of the thoracolumbar region for unrelated diagnostic indications. Materials and Methods: Patients with spinal abnormalities were excluded. Sagittal CT images of the thoracolumbar spine were obtained to calculate the DTC at T8–9, T9–10, and L1–2 interspaces. The measurements at all levels were obtained perpendicular to the long axis of the vertebral body. Statistical Analysis Used: Continuous data were depicted as mean with standard deviations. The categorical data were presented as counts with percentages. Results: The mean DTC distance at T8–9, T9–10, and L1–2 interspaces was 3.51 ± 0.98 mm (95% confidence interval [CI]: 3.35–3.67), 2.73 ± 0.94 mm (95% CI: 2.57–2.89), and 2.83 ± 1.08 mm (95% CI: 2.66–3.02), respectively. A significant difference was found between the genders at T9–10 (P = 0.02) and L1–2 levels (P = 0.04). No difference in DTC was found in toddlers, preschool children, school-going children, and adolescents. DTC at T8–9 showed a significant correlation with age (R2 = 0.0479; P = 0.04), weight (R2 = 0.038; P = 0.02), and height (R2 = 0.037; P = 0.03). Conclusion: Thoracic epidural space can be used in children and adolescents for epidural catheter placement. T8–9 level showed maximum DTC distance and significant correlation with age, height, and weight in CT imaging in the present study.
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Lee BJ, Jeong JH. Review: Steroid Use in Patients With Acute Spinal Cord Injury and Guideline Update. Korean J Neurotrauma 2022; 18:22-30. [PMID: 35557630 PMCID: PMC9064751 DOI: 10.13004/kjnt.2022.18.e21] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/05/2022] [Indexed: 11/15/2022] Open
Affiliation(s)
- Byung-Jou Lee
- Department of Neurosurgery and Neuroscience & Radiosurgery Hybrid Research Center, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Je Hoon Jeong
- Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
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Zeraatpisheh Z, Mirzaei E, Nami M, Alipour H, Ghasemian S, Azari H, Aligholi H. A New and Simple Method for Spinal Cord Injury Induction in Mice. Basic Clin Neurosci 2022; 13:47-56. [PMID: 36589023 PMCID: PMC9790099 DOI: 10.32598/bcn.2021.35.3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 03/05/2020] [Accepted: 07/12/2020] [Indexed: 01/04/2023] Open
Abstract
Introduction Spinal Cord Injury (SCI) is a devastating disease with poor clinical outcomes. Animal models provide great opportunities to expand our horizons in identifying SCI pathophysiological mechanisms and introducing effective treatment strategies. The present study introduces a new murine contusion model. Methods A simple, cheap, and reproducible novel instrument was designed, which consisted of a body part, an immobilization piece, and a bar-shaped weight. The injury was inflicted to the spinal cord using an 8-g weight for 5, 10, or 15 minutes after laminectomy at the T9 level in male C57BL/6 mice. Motor function, cavity formation, cell injury, and macrophage infiltration were evaluated 28 days after injury. Results The newly designed instrument minimized adverse spinal movement during injury induction. Moreover, no additional devices, such as a stereotaxic apparatus, were required to stabilize the animals during the surgical procedure. Locomotor activity was deteriorated after injury. Furthermore, tissue damage and cell injury were exacerbated by increasing the duration of weight exertion. In addition, macrophage infiltration around the injured tissue was observed 28 days after injury. Conclusion This novel apparatus could induce a controllable SCI with a clear cavity formation in mice. No accessory elements are needed, which can be used in future SCI studies. Highlights A simple and precise method has been introduced for creating Spinal Cord Injury (SCI) in mice by a novel device.The device consists of a body part, an immobilization piece, and a bar-shaped weight.Assessment of locomotor activity, tissue damage, and macrophage infiltration confirmed the capability of the new SCI method.Reduction of adverse spinal movements and working without any accessory elements are the key points of this new animal model of SCI. Plain Language Summary Spinal Cord Injury (SCI) is a medical problem that can cause the permanent motor and sensory dysfunction. Traffic accidents, falls, and violence are the most frequent causes of SCI, often affecting young people. Patients and even their families may encounter other problems, including reducing life quality, psychological burden, and enormous medical costs. Despite scientific and technological advances, no effective treatment has been found for SCI. Therefore, animal models help study damage mechanisms and evaluate novel treatment strategies. All SCI research centers require an economical and reproducible device without using complex surgical procedures by experienced surgeons to minimize variations in damage to the spinal cord. In this study, a simple, cheap, and reproducible novel instrument for SCI induction is introduced. The instrument consists of various parts, including a body part, an immobilization piece, and a bar-shaped weight. An 8-g weight was used for 5, 10, or 15 minutes to inflict injury to the spinal cord. Behavioral and tissue studies indicated that SCI could be induced in rodents in different severity without other elements. This instrument can be used in future investigations for SCI studies, including tissue engineering, stem cell therapy, and drugs delivery to access effective treatment.
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Affiliation(s)
- Zahra Zeraatpisheh
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Esmaeil Mirzaei
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Nami
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamed Alipour
- Department of Tissue Engineering & Applied cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Hassan Azari
- Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA
| | - Hadi Aligholi
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
- Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
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Xie X, Xiao Y, Xu K. Mechanism underlying circularRNA_014301-mediated regulation of neuronal cell inflammation and apoptosis. Exp Ther Med 2021; 22:1432. [PMID: 34707713 PMCID: PMC8543437 DOI: 10.3892/etm.2021.10867] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 08/25/2021] [Indexed: 11/05/2022] Open
Abstract
Spinal cord injury (SCI) causes damage to the spinal cord owing to trauma or disease and myelinated fiber tracts that transmit sensation and motor signals to and from the brain. Circular RNAs (circRNAs) are a recently discovered class of regulatory molecules, and their roles in SCI are still unknown. circRNA_014301 was indicated to be differentially expressed in the spinal cord at the site of SCI in a rat model. To analyze the role of circRNA_014301 in SCI, we exposed rat adrenal pheochromocytoma PC12 cells were exposed to increasing concentrations of lipopolysaccharide (LPS) and to construct a PC12 cell inflammatory model. Cell Counting Kit-8 assay was used to analyze cell viability. Reverse transcription-quantitative PCR and ELISA were used to detect the expression of inflammatory factors (IL-1β, IL-6 and TNF-α). Annexin V-FITC/PI double staining was employed to detect cell apoptosis, and western blotting was performed to detect the expression of apoptotic proteins (Bax/Bcl-2/cleaved caspase-3) and NF-κB. The results demonstrated that LPS induced inflammation in PC12 cells as evidenced by the reduced cell proliferation and enhanced expression of inflammatory and apoptotic factors under increasing LPS concentrations. Western blotting analyses indicated that circRNA_014301 induced the expression of p-NF-κB/NF-κB, Bax and cleaved caspase-3, and decreased the expression of Bcl-2 following LPS-induced inflammation, and this apoptosis-promoting effect was relieved by small interfering-RNA-mediated knockdown of circRNA_014301. Thus, circRNA_014301 silencing alleviated apoptosis and inflammation in PC12 cells. SCI is invariably associated with spinal cord inflammation, and LPS was used to stimulate apoptosis and inflammatory injury in PC12 cells, and create a cell model of SCI. By promoting PC12 cell apoptosis under inflammatory conditions, it was indicated that circRNA_014301 may suppress SCI. Therefore, circRNA_014301 may represent a potential target for SCI diagnosis and therapy.
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Affiliation(s)
- Xiankuan Xie
- Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310053, P.R. China
| | - Yuxiang Xiao
- Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310053, P.R. China
| | - Kan Xu
- Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310053, P.R. China
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36
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Zhu J, Li L, Ding J, Huang J, Shao A, Tang B. The Role of Formyl Peptide Receptors in Neurological Diseases via Regulating Inflammation. Front Cell Neurosci 2021; 15:753832. [PMID: 34650406 PMCID: PMC8510628 DOI: 10.3389/fncel.2021.753832] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/02/2021] [Indexed: 01/02/2023] Open
Abstract
Formyl peptide receptors (FPRs) are a group of G protein-coupled cell surface receptors that play important roles in host defense and inflammation. Owing to the ubiquitous expression of FPRs throughout different cell types and since they interact with structurally diverse chemotactic agonists, they have a dual function in inflammatory processes, depending on binding with different ligands so that accelerate or inhibit key intracellular kinase-based regulatory pathways. Neuroinflammation is closely associated with the pathogenesis of neurodegenerative diseases, neurogenic tumors and cerebrovascular diseases. From recent studies, it is clear that FPRs are important biomarkers for neurological diseases as they regulate inflammatory responses by monitoring glial activation, accelerating neural differentiation, regulating angiogenesis, and controlling blood brain barrier (BBB) permeability, thereby affecting neurological disease progression. Given the complex mechanisms of neurological diseases and the difficulty of healing, we are eager to find new and effective therapeutic targets. Here, we review recent research about various mechanisms of the effects generated after FPR binding to different ligands, role of FPRs in neuroinflammation as well as the development and prognosis of neurological diseases. We summarize that the FPR family has dual inflammatory functional properties in central nervous system. Emphasizing that FPR2 acts as a key molecule that mediates the active resolution of inflammation, which binds with corresponding receptors to reduce the expression and activation of pro-inflammatory composition, govern the transport of immune cells to inflammatory tissues, and restore the integrity of the BBB. Concurrently, FPR1 is essentially related to angiogenesis, cell proliferation and neurogenesis. Thus, treatment with FPRs-modulation may be effective for neurological diseases.
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Affiliation(s)
- Jiahui Zhu
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lingfei Li
- Department of Neurology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiao Ding
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jinyu Huang
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Anwen Shao
- Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Bo Tang
- Department of Neurology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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A review of emerging neuroprotective and neuroregenerative therapies in traumatic spinal cord injury. Curr Opin Pharmacol 2021; 60:331-340. [PMID: 34520943 DOI: 10.1016/j.coph.2021.08.009] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 08/04/2021] [Indexed: 11/20/2022]
Abstract
Traumatic spinal cord injuries (SCIs) have far-reaching physical, social, and financial consequences. While medical advancements have improved supportive therapeutic measures for SCI patients, no effective neuroregenerative therapeutic options exist to date. Instead, the paradigm of SCI therapy is inevitably directed towards damage control rather than the restoration of a state of functional independence. Facing a continuous increase in the prevalence of spinal cord injured patients, neuroprotective and neuroregenerative strategies have earned tremendous scientific interest. This review intends to provide a robust summary of the most promising neuroprotective and neuroregenerative therapies currently under investigation. While we highlight encouraging neuroprotective strategies as well, the focus of this review lies on neuroregenerative therapies, including neuropharmacological and cell-based approaches. We finally point to the exciting investigational areas of biomaterial scaffolds and neuromodulation therapies.
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38
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Dai N, Tang C, Liu H, Huang S. Effect of electroacupuncture on inhibition of inflammatory response and oxidative stress through activating ApoE and Nrf2 in a mouse model of spinal cord injury. Brain Behav 2021; 11:e2328. [PMID: 34423582 PMCID: PMC8442587 DOI: 10.1002/brb3.2328] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 07/16/2021] [Accepted: 08/02/2021] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Electroacupuncture protects neurons and myelinated axons after spinal cord injury by mitigating the inflammatory response and oxidative stress, but how it exerts these effects is unclear. METHODS AND RESULTS Spinal cord injury was induced in C57BL/6 wild-type and apolipoprotein E (ApoE) knockout (ApoE-/- ) mice, followed by electroacupuncture or ApoE mimetic peptide COG112 treatment. Mice with spinal cord injury suffered loss of myelinated axons and hindlimb motor function through the detections of Basso mouse scale, histology, and transmission electron microscopy; electroacupuncture partially reversed these effects in wild-type mice but not in ApoE-/- mice. Combining exogenous ApoE administration with electroacupuncture significantly mitigated the effects of spinal cord injury in both mouse strains, and these effects were associated with up-regulation of anti-inflammatory cytokines and down-regulation of pro-inflammatory cytokines which were detected by quantitative reverse transcription-polymerase chain reaction. Combination treatment also reduced oxidative stress by up-regulating ApoE and Nrf2/HO-1 signaling pathway through the detections of immunofluorescence and western blot analysis. CONCLUSIONS These results suggest that electroacupuncture protects neurons and myelinated axons following spinal cord injury through an ApoE-dependent mechanism.
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Affiliation(s)
- Ni Dai
- Traditional Chinese Medicine College, Chongqing Medical University, Chongqing, China
| | - Chenglin Tang
- Traditional Chinese Medicine College, Chongqing Medical University, Chongqing, China
| | - Hui Liu
- Institute of Neuroscience, Chongqing Medical University, Chongqing, China
| | - Siqin Huang
- Traditional Chinese Medicine College, Chongqing Medical University, Chongqing, China
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Gilmour AD, Reshamwala R, Wright AA, Ekberg JAK, St John JA. Optimizing Olfactory Ensheathing Cell Transplantation for Spinal Cord Injury Repair. J Neurotrauma 2021; 37:817-829. [PMID: 32056492 DOI: 10.1089/neu.2019.6939] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Cell transplantation constitutes an important avenue for development of new treatments for spinal cord injury (SCI). These therapies are aimed at supporting neural repair and/or replacing lost cells at the injury site. To date, various cell types have been trialed, with most studies focusing on different types of stem cells or glial cells. Here, we review commonly used cell transplantation approaches for spinal cord injury (SCI) repair, with focus on transplantation of olfactory ensheathing cells (OECs), the glial cells of the primary olfactory nervous system. OECs are promising candidates for promotion of neural repair given that they support continuous regeneration of the olfactory nerve that occurs throughout life. Further, OECs can be accessed from the nasal mucosa (olfactory neuroepithelium) at the roof of the nasal cavity and can be autologously transplanted. OEC transplantation has been trialed in many animal models of SCI, as well as in human clinical trials. While several studies have been promising, outcomes are variable and the method needs improvement to enhance aspects such as cell survival, integration, and migration. As a case study, we include the approaches used by our team (the Clem Jones Centre for Neurobiology and Stem Cell Research, Griffith University, Nathan, QLD, Australia) to address the current problems with OEC transplantation and discuss how the therapeutic potential of OEC transplantation can be improved. Our approach includes discovery research to improve our knowledge of OEC biology, identifying natural and synthetic compounds to stimulate the neural repair properties of OECs, and designing three-dimensional cell constructs to create stable and transplantable cell structures.
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Affiliation(s)
- Aaron D Gilmour
- Clem Jones Centre for Neurobiology and Stem Cell Research and Griffith University, Nathan, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia
| | - Ronak Reshamwala
- Clem Jones Centre for Neurobiology and Stem Cell Research and Griffith University, Nathan, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia.,Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia
| | - Alison A Wright
- Clem Jones Centre for Neurobiology and Stem Cell Research and Griffith University, Nathan, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia
| | - Jenny A K Ekberg
- Clem Jones Centre for Neurobiology and Stem Cell Research and Griffith University, Nathan, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia.,Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia
| | - James A St John
- Clem Jones Centre for Neurobiology and Stem Cell Research and Griffith University, Nathan, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia.,Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia
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40
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The Application of an Omentum Graft or Flap in Spinal Cord Injury. Int J Mol Sci 2021; 22:ijms22157930. [PMID: 34360697 PMCID: PMC8347514 DOI: 10.3390/ijms22157930] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 07/16/2021] [Accepted: 07/21/2021] [Indexed: 12/16/2022] Open
Abstract
Background: Spinal cord injury (SCI) causes a primary injury at the lesion site and triggers a secondary injury and prolonged inflammation. There has been no definitive treatment till now. Promoting angiogenesis is one of the most important strategies for functional recovery after SCI. The omentum, abundant in blood and lymph vessels, possesses the potent ability of tissue regeneration. Methods: The present work examines the efficacy of autologous omentum, either as a flap (with vascular connection intact) or graft (severed vascular connection), on spinal nerve regeneration. After contusive SCI in rats, a thin sheath of omentum was grafted to the injured spinal cord. Results: Omental graft improved behavior scores significantly from the 3rd to 6th week after injury (6th week, 5.5 ± 0.5 vs. 8.6 ± 1.3, p < 0.05). Furthermore, the reduction in cavity and the preservation of class III β-tubulin-positive nerve fibers in the injury area was noted. Next, the free omental flap was transposed to a completely transected SCI in rats through a pre-implanted tunnel. The flap remained vascularized and survived well several weeks after the operation. At 16 weeks post-treatment, SCI rats with omentum flap treatment displayed the preservation of significantly more nerve fibers (p < 0.05) and a reduced injured cavity, though locomotor scores were similar. Conclusions: Taken together, the findings of this study indicate that treatment with an omental graft or transposition of an omental flap on an injured spinal cord has a positive effect on nerve protection and tissue preservation in SCI rats. The current data highlight the importance of omentum in clinical applications.
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Zeraatpisheh Z, Mirzaei E, Nami M, Alipour H, Mahdavipour M, Sarkoohi P, Torabi S, Azari H, Aligholi H. Local delivery of fingolimod through PLGA nanoparticles and PuraMatrix-embedded neural precursor cells promote motor function recovery and tissue repair in spinal cord injury. Eur J Neurosci 2021; 54:5620-5637. [PMID: 34251711 DOI: 10.1111/ejn.15391] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 12/19/2022]
Abstract
Spinal cord injury (SCI) is a devastating clinical problem that can lead to permanent motor dysfunction. Fingolimod (FTY720) is a sphingosine structural analogue, and recently, its therapeutic benefits in SCI have been reported. The present study aimed to evaluate the therapeutic efficacy of fingolimod-incorporated poly lactic-co-glycolic acid (PLGA) nanoparticles (nanofingolimod) delivered locally together with neural stem/progenitor cells (NS/PCs) transplantation in a mouse model of contusive acute SCI. Fingolimod was encapsulated in PLGA nanoparticles by the emulsion-evaporation method. Mouse NS/PCs were harvested and cultured from embryonic Day 14 (E14) ganglionic eminences. Induction of SCI was followed by the intrathecal delivery of nanofingolimod with and without intralesional transplantation of PuraMatrix-encapsulated NS/PCs. Functional recovery, injury size and the fate of the transplanted cells were evaluated after 28 days. The nanofingolimod particles represented spherical morphology. The entrapment efficiency determined by UV-visible spectroscopy was approximately 90%, and the drug content of fingolimod loaded nanoparticles was 13%. About 68% of encapsulated fingolimod was slowly released within 10 days. Local delivery of nanofingolimod in combination with NS/PCs transplantation led to a stronger improvement in neurological functions and minimized tissue damage. Furthermore, co-administration of nanofingolimod and NS/PCs not only increased the survival of transplanted cells but also promoted their fate towards more oligodendrocytic phenotype. Our data suggest that local release of nanofingolimod in combination with three-dimensional (3D) transplantation of NS/PCs in the acute phase of SCI could be a promising approach to restore the damaged tissues and improve neurological functions.
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Affiliation(s)
- Zahra Zeraatpisheh
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.,Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Esmaeil Mirzaei
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.,Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Nami
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.,Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamed Alipour
- Department of Tissue Engineering and Applied cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Marzieh Mahdavipour
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Sarkoohi
- Department of Pharmacology and Toxicology, School of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Somayyeh Torabi
- Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hassan Azari
- Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
| | - Hadi Aligholi
- Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.,Neuroscience Laboratory (Brain, Cognition and Behavior), Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
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Javdani M, Ghorbani R, Hashemnia M. Histopathological Evaluation of Spinal Cord with Experimental Traumatic Injury Following Implantation of a Controlled Released Drug Delivery System of Chitosan Hydrogel Loaded with Selenium Nanoparticle. Biol Trace Elem Res 2021; 199:2677-2686. [PMID: 32959339 DOI: 10.1007/s12011-020-02395-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 09/13/2020] [Indexed: 10/23/2022]
Abstract
The purpose of this study was to evaluate the neuroprotective effect of local implantation of a controlled delivery system of chitosan hydrogel loaded with selenium nanoparticles in rats with spinal cord injury (SCI). For this purpose, 60 adult female rats were randomly divided into three equal groups. In all three groups, SCI was induced by aneurysm clamping at the level of thoracic vertebrae under inhaled anesthesia with isoflurane. In one group after spinal cord injury, chitosan hydrogels loaded with selenium nanoparticles (treatment group), and in the other group, only chitosan hydrogels (positive control group) were placed at the site of injury. In the last group (negative control), no material was placed in the injury site. Hematoxylin-eosin and glial fibrillary acidic protein (GFAP) staining evaluated histological changes at the site of injury on days 3, 7, 21, and 28 after surgery. Evaluations show that hemorrhage and inflammation also have a marked decrease in inflammatory cells at different times in the treatment group. This decrease was also seen in the chitosan group but was less severe than in the treatment group. The formation of nerve fibers was also observed in the treatment group over time of injury. Immunohistochemical studies of damaged tissue showed higher expression of GFAP protein in the astrocytes of the treatment group than in the other two groups and the chitosan group compared with the negative control group. A controlled drug delivery system containing selenium nanoparticles seems to play a role in the protection of nerve cells through its anti-inflammatory effect.
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Affiliation(s)
- Moosa Javdani
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, 115, Shahrekord, Iran.
| | - Roya Ghorbani
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, 115, Shahrekord, Iran
| | - Mohammad Hashemnia
- Department of Pathobiology, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
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Zhang H, Zhang W, Bai G, Gao L, Li K. Bone Morphogenetic Protein-7 (BMP-7) Promotes Neuronal Differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs) In Vitro. BIOMED RESEARCH INTERNATIONAL 2021; 2021:7239783. [PMID: 33575343 PMCID: PMC7857886 DOI: 10.1155/2021/7239783] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 12/15/2020] [Accepted: 01/16/2021] [Indexed: 11/18/2022]
Abstract
This study is aimed at investigating the effects of bone morphogenetic protein-7 (BMP-7) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells in vitro. The rat BMSCs were isolated and identified, which were divided into the control, empty, recombinant rhBMP-7 transfection, and Lv-BMP-7 transfection groups. BMSCs were induced under different conditions. CCK-8 assay was performed to detect cell proliferation. ALP was used to detect cell activity. Cellular morphology after induction was observed. Immunofluorescence was conducted to detect the expression and location of nerve cell markers. Quantitative real-time PCR and Western blot analysis were performed to detect the mRNA and protein expression levels, respectively. The rhBMP-7 and Lv-BMP-7 promoted the proliferation of BMSCs, accompanied with increased ALP activities. Morphological observations revealed that rhBMP-7 and Lv-BMP-7 induced BMSCs to differentiate into neuron-like cells. Immunofluorescence revealed that the rhBMP-7 and Lv-BMP-7 groups showed positive expression of MAP-2 and Nfh in BMSCs. MAP-2 was mainly distributed in the cell body and cellular protrusion, while Nfh was mainly distributed in the cytoplasm and cell protrusion. Positive mRNA and protein expressions of MAP-2 and Nfh were observed in the cells of the rhBMP-7 and Lv-BMP-7 groups, and the expression levels were significantly higher than the control and empty groups. Both exogenous BMP-7 (rhBMP-7) and endogenous BMP-7 (Lv-BMP-7) can induce BMSCs to differentiate into neuron-like cells highly expressing the neuronal markers MAP-2 and Nfh.
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Affiliation(s)
- Heng Zhang
- Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical College, Laboratory of Tissue and Transplant in Anhui Province, Bengbu Medical College, Bengbu City, China
| | - Wen Zhang
- Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Shihezi University, Xinjiang, China
| | - Guangchao Bai
- Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Shihezi University, Xinjiang, China
| | - Lei Gao
- Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Shihezi University, Xinjiang, China
| | - Kuanxin Li
- Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical College, Laboratory of Tissue and Transplant in Anhui Province, Bengbu Medical College, Bengbu City, China
- Department of Orthopaedics, The Second Affiliated Hospital of Medical College, Shihezi University, Xinjiang, China
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Jeong HJ, Yun Y, Lee SJ, Ha Y, Gwak SJ. Biomaterials and strategies for repairing spinal cord lesions. Neurochem Int 2021; 144:104973. [PMID: 33497713 DOI: 10.1016/j.neuint.2021.104973] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/17/2021] [Accepted: 01/18/2021] [Indexed: 01/13/2023]
Abstract
Spinal cord injury (SCI) causes intractable disease and leads to inevitable physical, financial, and psychological burdens on patients and their families. SCI is commonly divided into primary and secondary injury. Primary injury occurs upon direct impact to the spinal cord, which leads to cell necrosis, axon disruption, and vascular loss. This triggers pathophysiological secondary injury, which has several phases: acute, subacute, intermediate, and chronic. These phases are dependent on post-injury time and pathophysiology and have various causes, such as the infiltration of inflammatory cells and release of cytokines that can act as a barrier to neural regeneration. Another unique feature of SCI is the glial scar produced from the reactive proliferation of astrocytes, which acts as a barrier to axonal regeneration. Interdisciplinary research is investigating the use of biomaterials and tissue-engineered fabrication to overcome SCI. In this review, we discuss representative biomaterials, including natural and synthetic polymers and nanomaterials. In addition, we describe several strategies to repair spinal cord injuries, such as fabrication and the delivery of therapeutic biocomponents. These biomaterials and strategies may offer beneficial information to enhance the repair of spinal cord lesions.
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Affiliation(s)
- Hun-Jin Jeong
- Department of Mechanical Engineering, Wonkwang University, 54538, Iksan, Republic of Korea
| | - Yeomin Yun
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, Republic of Korea
| | - Seung-Jae Lee
- Department of Mechanical Engineering, Wonkwang University, 54538, Iksan, Republic of Korea; Department of Mechanical and Design Engineering, Wonkwang University, 54538, Iksan, Republic of Korea
| | - Yoon Ha
- Department of Neurosurgery, Spine and Spinal Cord Institute, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, Republic of Korea; POSTECH Biotech Center, Pohang University of Science and Technology, San 31, Pohang, Gyeongbuk, Republic of Korea
| | - So-Jung Gwak
- Department of Chemical Engineering, Wonkwang University, 54538, Iksan, Republic of Korea.
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Goldshmit Y, Banyas E, Bens N, Yakovchuk A, Ruban A. Blood glutamate scavengers and exercises as an effective neuroprotective treatment in mice with spinal cord injury. J Neurosurg Spine 2020; 33:692-704. [PMID: 32619986 DOI: 10.3171/2020.4.spine20302] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 04/16/2020] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Excitotoxicity due to neuronal damage and glutamate release is one of the first events that leads to the progression of neuronal degeneration and functional impairment. This study is based on a paradigm shift in the therapeutic approach for treating spinal cord injury (SCI). The authors tested a new treatment targeting removal of CNS glutamate into the blood circulation by injection of the blood glutamate scavengers (BGSs) recombinant enzyme glutamate-oxaloacetate transaminase (rGOT1) and its cosubstrate oxaloacetic acid (OxAc). Their primary objective was to investigate whether BGS treatment, followed by treadmill exercises in mice with SCI, could attenuate excitotoxicity, inflammation, scarring, and axonal degeneration and, at a later time point, improve functional recovery. METHODS A pharmacokinetic experiment was done in C57BL/6 naive mice to verify rGOT1/OxAc blood activity and to characterize the time curve of glutamate reduction in the blood up to 24 hours. The reduction of glutamate in CSF after BGS administration in mice with SCI was confirmed by high-performance liquid chromatography. Next, SCI (left hemisection) was induced in the mice, and the mice were randomly assigned to one of the following groups at 1 hour postinjury: control (underwent SCI and received PBS), treadmill exercises, rGOT1/OxAc treatment, or rGOT1/OxAc treatment followed by treadmill exercises. Treatment started 1 hour postinjury with an injection of rGOT1/OxAc and continued for 5 consecutive days. Starting 1 week after SCI, the exercises and the combined treatment groups recommenced the treadmill exercise regimen 5 days a week for 3 months. Locomotor function was assessed for 3 months using the horizontal grid walking test and CatWalk. Axonal anterograde and wallerian degenerations were evaluated using tetramethylrhodamine dextran. Tissue sections were immunofluorescently stained for Iba1, GFAP, GAP-43, synaptophysin, and NeuN. RESULTS BGS treatment decreased the CSF glutamate level up to 50%, reduced axonal wallerian degeneration, and increased axonal survival and GAP-43 expression in neuronal cells. Combined treatment reduced inflammation, scarring, and lesion size. Additionally, the combination of BGS treatment and exercises increased synapses around motor neurons and enhanced axonal regeneration through the lesion site. This resulted in motor function improvement 3 months post-SCI. CONCLUSIONS As shown by biochemical, immunohistochemical, and functional analysis, BGSs exhibit a substantial neuroprotective effect by reducing excitotoxicity and secondary damage after SCI. Furthermore, in combination with exercises, they reduced axonal degeneration and scarring and resulted in improved functional recovery.
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Affiliation(s)
- Yona Goldshmit
- 1Steyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- 2Australian Regenerative Medicine Institute, Monash Biotechnology, Clayton, Victoria, Australia; and
| | - Evgeni Banyas
- 1Steyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nicole Bens
- 1Steyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Alex Yakovchuk
- 1Steyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Angela Ruban
- 1Steyer School of Health Professions, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- 3Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
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Zhang X, Jing Y, Qin C, Liu C, Yang D, Gao F, Yang M, Du L, Li J. Mechanical stress regulates autophagic flux to affect apoptosis after spinal cord injury. J Cell Mol Med 2020; 24:12765-12776. [PMID: 32945105 PMCID: PMC7686991 DOI: 10.1111/jcmm.15863] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/28/2020] [Accepted: 08/17/2020] [Indexed: 12/21/2022] Open
Abstract
Increased mechanical stress after spinal cord injury (SCI) expands the scope of nerve tissue damage and exacerbates nerve function defects. Surgical decompression after SCI is a conventional therapeutic strategy and has been proven to have neuroprotective effects. However, the mechanisms of the interaction between mechanical stress and neurons are currently unknown. In this study, we monitored intramedullary pressure (IMP) and investigated the therapeutic benefit of decompression (including durotomy and piotomy) after injury and its underlying mechanisms in SCI. We found that decreased IMP promotes the generation and degradation of LC3 II, promotes the degradation of p62 and enhances autophagic flux to alleviate apoptosis. The lysosomal dysfunction was reduced after decompression. Piotomy was better than durotomy for the histological repair of spinal cord tissue after SCI. However, the autophagy‐lysosomal pathway inhibitor chloroquine (CQ) partially reversed the apoptosis inhibition caused by piotomy after SCI, and the structural damage was also aggravated after CQ administration. An antibody microarray analysis showed that decompression may reverse the up‐regulated abundance of p‐PI3K, p‐AKT and p‐mTOR caused by SCI. Our findings may contribute to a better understanding of the mechanism of decompression and the effects of mechanical stress on autophagy after SCI.
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Affiliation(s)
- Xin Zhang
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Yingli Jing
- China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.,Institute of Rehabilitation medicine, China Rehabilitation Research Center, Beijing, China
| | - Chuan Qin
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Changbin Liu
- Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Beijing, China
| | - Degang Yang
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Feng Gao
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Mingliang Yang
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Liangjie Du
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
| | - Jianjun Li
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China.,China Rehabilitation Science Institute, Beijing, China.,Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.,Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.,Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China
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Kandalam S, De Berdt P, Ucakar B, Vanvarenberg K, Bouzin C, Gratpain V, Diogenes A, Montero-Menei CN, des Rieux A. Human dental stem cells of the apical papilla associated to BDNF-loaded pharmacologically active microcarriers (PAMs) enhance locomotor function after spinal cord injury. Int J Pharm 2020; 587:119685. [PMID: 32712253 DOI: 10.1016/j.ijpharm.2020.119685] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/14/2020] [Accepted: 07/20/2020] [Indexed: 02/08/2023]
Abstract
There is no treatment for spinal cord injury (SCI) that fully repairs the damages. One strategy is to inject mesenchymal stem cells around the lesion to benefit from their immunomodulatory properties and neuroprotective effect. Our hypothesis was that the combination of dental stem cells from the apical papilla (SCAP) with pharmacologically active microcarriers (PAMs) releasing brain-derived neurotrophic factor (BDNF) would improve rat locomotor function by immunomodulation and neuroprotection. BDNF-PAMs were prepared by solid/oil/water emulsion of poly(L-lactide-co-glycolide) and nanoprecipitated BDNF and subsequent coating with fibronectin. SCAP were then seeded on BDNF-PAMs. SCAP expression of neuronal and immunomodulatory factors was evaluated in vitro. SCAP BDNF-PAMs were injected in a rat spinal cord contusion model and their locomotor function was evaluated by Basso, Beattie, and Bresnahan (BBB) scoring. Impact on inflammation and neuroprotection/axonal growth was evaluated by immunofluorescence. Culture on PAMs induced the overexpression of immunomodulatory molecules and neural/neuronal markers. Injection of SCAP BDNF-PAMs at the lesion site improved rat BBB scoring, reduced the expression of inducible nitric oxide synthase and increased the expression of βIII tubulin, GAP43, and 5-HT. These results confirm the suitability and versatility of PAMs as combined drug and cell delivery system for regenerative medicine applications but also that BDNF-PAMs potentialize the very promising therapeutic potential of SCAP in the scope of SCI.
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Affiliation(s)
- Saikrishna Kandalam
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium; CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers F-49933, France
| | - Pauline De Berdt
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Bernard Ucakar
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Kevin Vanvarenberg
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Caroline Bouzin
- IREC Imaging platform (2IP), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, UCLouvain, IREC, 1200 Brussels, Belgium
| | - Viridiane Gratpain
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium
| | - Anibal Diogenes
- Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
| | | | - Anne des Rieux
- Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Université Catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium.
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Lu Y, Yang J, Wang X, Ma Z, Li S, Liu Z, Fan X. Research progress in use of traditional Chinese medicine for treatment of spinal cord injury. Biomed Pharmacother 2020; 127:110136. [PMID: 32335299 DOI: 10.1016/j.biopha.2020.110136] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/17/2020] [Accepted: 03/30/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Spinal cord injury (SCI) is a serious central nervous system disorder caused by trauma that has gradually become a major challenge in clinical medical research. As an important branch of worldwide medical research, traditional Chinese medicine (TCM) is rapidly moving towards a path of reform and innovation. Therefore, this paper systematically reviews research related to existing TCM treatments for SCI, with the aims of identifying deficits and shortcomings within the field, and proposing feasible alternative prospects. METHODS All data and conclusions in this paper were obtained from articles published by peers in relevant fields. PubMed, SciFinder, Google Scholar, Web of Science, and CNKI databases were searched for relevant articles. Results regarding TCM for SCI were identified and retrieved, then manually classified and selected for inclusion in this review. RESULTS The literature search identified a total of 652 articles regarding TCM for SCI. Twenty-eight treatments (16 active ingredients, nine herbs, and three compound prescriptions) were selected from these articles; the treatments have been used for the prevention and treatment of SCI. In general, these treatments involved antioxidative, anti-inflammatory, neuroprotective, and/or antiapoptotic effects of TCM compounds. CONCLUSIONS This paper showed that TCM treatments can serve as promising auxiliary therapies for functional recovery of patients with SCI. These findings will contribute to the development of diversified treatments for SCI.
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Affiliation(s)
- Yubao Lu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China
| | - Jingjing Yang
- The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China
| | - Xuexi Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Zhanjun Ma
- The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu 730000, China.
| | - Sheng Li
- Lanzhou First People's Hospital, Lanzhou, Gansu 730000, China
| | - Zhaoyang Liu
- Department of Medical Imaging, Shanxi Medical University, Jinzhong, Shanxi 030600, China
| | - Xuegong Fan
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, China
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Ullah S, Qureshi AZ, Tantawy SS, AlJaizani YA. An unusual mechanism of spinal cord injury due to active neck stretching and its functional implications. Clin Case Rep 2020; 8:1090-1093. [PMID: 32577272 PMCID: PMC7303884 DOI: 10.1002/ccr3.2831] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 03/03/2020] [Accepted: 03/12/2020] [Indexed: 11/24/2022] Open
Abstract
Spinal cord injury without radiological abnormality is a rare entity and has not been reported to occur secondary to active neck stretching. The case report highlights the possible mechanisms of injury and functional outcomes of multidisciplinary rehabilitation.
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Affiliation(s)
- Sami Ullah
- Department of Physical Medicine & RehabilitationKing Fahad Medical CityRiyadhSaudi Arabia
| | - Ahmad Zaheer Qureshi
- Department of Physical Medicine & RehabilitationKing Fahad Medical CityRiyadhSaudi Arabia
| | - Sherif Samir Tantawy
- Department of Physical Medicine & RehabilitationKing Fahad Medical CityRiyadhSaudi Arabia
| | - Yazid Antar AlJaizani
- Department of Physical Medicine & RehabilitationKing Fahad Medical CityRiyadhSaudi Arabia
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50
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Mohammed I, Ijaz S, Mokhtari T, Gholaminejhad M, Mahdavipour M, Jameie B, Akbari M, Hassanzadeh G. Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation. Metab Brain Dis 2020; 35:809-818. [PMID: 32185593 DOI: 10.1007/s11011-020-00563-w] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 03/05/2020] [Indexed: 12/17/2022]
Abstract
Spinal cord injury (SCI) is the destruction of spinal cord motor and sensory resulted from an attack on the spinal cord, which can cause significant physiological damage. The inflammasome is a multiprotein oligomer resulting in inflammation; the NLRP3 inflammasome composed of NLRP3, apoptosis-associated speck-like protein (ASC), procaspase-1, and cleavage of procaspase-1 into caspase-1 initiates the inflammatory response. Subventricular Zone (SVZ) is the origin of neural stem/progenitor cells (NS/PCs) in the adult brain. Extracellular vesicles (EVs) are tiny lipid membrane bilayer vesicles secreted by different types of cells playing an important role in cell-cell communications. The aim of this study was to investigate the effect of intrathecal transplantation of EVs on the NLRP3 inflammasome formation in SCI rats. Male wistar rats were divided into three groups as following: laminectotomy group, SCI group, and EVs group. EVs was isolated from SVZ, and characterized by western blot and DLS, and then injected into the SCI rats. Real-time PCR and western blot were carried out for gene expression and protein level of NLRP3, ASC, and Caspase-1. H&E and cresyl violet staining were performed for histological analyses, as well as BBB test for motor function. The results indicated high level in mRNA and protein level in SCI group in comparison with laminectomy (p < 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI (p < 0.001). H&E and cresyl violet staining showed recovery in neural cells of spinal cord tissue in EVs group in comparison with SCI group. BBB test showed the promotion of motor function in EVs group compared to SCI in 14 days (p < 0.05). We concluded that the injection of EVs could recover the motor function in rats with SCI and rescue the neural cells of spinal cord tissue by suppressing the formation of the NLRP3 inflammasome complex.
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Affiliation(s)
- Ibrahim Mohammed
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Ijaz
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Tahmineh Mokhtari
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Morteza Gholaminejhad
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Marzieh Mahdavipour
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Behnamedin Jameie
- Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Akbari
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Gholamreza Hassanzadeh
- Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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