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Yang Y, Gu W, Xu S, Wang S, Shi H, Zhang L, Meng XG, Hong F, Du Y. Treatment for peripheral nerve injury: a protocol for a systematic review and Bayesian network meta-analysis. BMJ Open 2024; 14:e090497. [PMID: 39732487 PMCID: PMC11683916 DOI: 10.1136/bmjopen-2024-090497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 11/11/2024] [Indexed: 12/30/2024] Open
Abstract
INTRODUCTION Available therapies for peripheral nerve injury (PNI) include surgical and non-surgical treatments. Surgical treatment includes neurorrhaphy, grafting (allografts and autografts) and tissue-engineered grafting (artificial nerve guide conduits), while non-surgical treatment methods include electrical stimulation, magnetic stimulation, laser phototherapy and administration of nerve growth factors. However, the treatments currently available to best manage the different PNI manifestations remain undetermined. This systematic review and network meta-analysis (NMA) aims to address this and determine the best treatment or combination of treatments for PNI. METHODS AND ANALYSIS A comprehensive search of MEDLINE (via PubMed), Embase, Cochrane Library, Web of Science, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, Wanfang Database, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and the Chinese Clinical Trial Register will be completed using the following keywords: peripheral nerve injury, therapies and related entry terms. Studies will be included based on specific eligibility criteria, and the reference lists of the included studies will be manually searched. Relevant data will be extracted from the included studies using a specially designed data extraction sheet. The risk of bias in the included studies will be assessed, and the overall strength of the evidence will be summarised. A random-effects model was used for all pairwise meta-analyses (95% CI). Bayesian NMA is used to explore the relative benefits of various treatments. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating NMA statement. ETHICS AND DISSEMINATION As the protocol for this systematic review and Bayesian NMA is based on studies with published results and does not involve patient interventions, no ethical review is required. The results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42023475135.
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Affiliation(s)
- Yongke Yang
- Beilun District People's Hospital, Ningbo, China
| | - Wenlong Gu
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shuting Xu
- Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Shuai Wang
- Shijiazhuang Gaocheng Hospital of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei Province, China
| | - Huiyan Shi
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Lili Zhang
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiang-gang Meng
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Feng Hong
- Beilun District People's Hospital, Ningbo, China
| | - Yuzheng Du
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Wang Y, Yang S, Li B, Shuai C, Xiong X, Lu J. Epidemiology, risk factors, diagnosis, and treatment of intra-abdominal traumatic neuromas - a narrative review. BMC Gastroenterol 2023; 23:416. [PMID: 38017468 PMCID: PMC10683309 DOI: 10.1186/s12876-023-03049-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 11/09/2023] [Indexed: 11/30/2023] Open
Abstract
Traumatic neuroma (TN) is a disorganized proliferation of injured nerves arising from the axons and Schwann cells. Although TN rarely occurs in the abdominal cavity, the incidence of TN may be underestimated because of the large number of asymptomatic patients. TN can cause persistent pain, which seriously affects quality of life. TN of the biliary system can cause bile duct obstruction, leading to acute cholangitis. It is difficult to differentiate TN from malignancies or recurrence of malignancy, which results in a number of patients receiving aggressive treatment. We collected cases reports of intra-abdominal TN over the past 30 years form PubMed and cases diagnosed in our medical center over the past 20 years, which is the largest case series of intra-abdominal TN to the best of our knowledge. In this review, we discuss the epidemiology, pathophysiology, risk factors, classification, diagnosis, and management of intra-abdominal TN.
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Affiliation(s)
- Yaoqun Wang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Sishu Yang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Bei Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Cunyong Shuai
- Department of Hepatobiliary Surgery, Sichuan Provincial Corps Hospital, Chinese People's Armed Police Forces, Leshan, China.
| | - Xianze Xiong
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
| | - Jiong Lu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
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Chen Y, Pan Z, Meng F, Yu X, Xu Q, Huang L, Liang Q, Wu Y, Lin X. Magnetic resonance imaging assessment of the therapeutic effect of combined electroacupuncture and stem cells in acute peripheral nerve injury. Front Cell Neurosci 2022; 16:1065557. [PMID: 36605615 PMCID: PMC9807880 DOI: 10.3389/fncel.2022.1065557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022] Open
Abstract
Objectives: This study aimed to evaluate the therapeutic effect of a combination of Bone Mesenchymal stem cells (BMSCs) transplantation and Electroacupuncture (EA) for acute sciatic nerve injury in rats using magnetic resonance. Methods: Ninety-two male adult healthy Sprague-Dawley rats were randomly divided into the EA+BMSCs group, EA group, MSCs group, and PBS group (control). Electroacupuncture was performed on a rat receiving EA treatment at Huantiao (GB30) and Zusanli (ST36). T2 values and diffusion tensor imaging (DTI) derived from multiparametric magnetic resonance imaging (MRI), histological assessments, and immunohistochemistry was used to monitor nerve regeneration. Walking track analysis was used to assess nerve functional recovery. Repeated-measures one-way analysis of variance was used to evaluate the significance of T2, DTI, and SFI values among the four groups. One-way analysis of variance was used for comparing the histological characteristics. Bonferroni test was used for multiple pairwise comparisons at each time point. Results: In terms of FA, the EA+BMSCs and EA groups had faster recovery than PBS (control) in all time points after surgery, and the EA+BMSCs group recovered better than the BMSCs group at 3 weeks (P ≤ 0.008). FA values were higher in the EA group than in the BMSCs group at 4 weeks (P ≤ 0.008). In terms of RD, the EA+BMSCs group recovered better than the BMSCs group at 2 and 4 weeks (P ≤ 0.008). Immunofluorescence staining for axon guidance molecule netrin-1 revealed that it was significantly higher in the EA+BMSCs subgroup and EA subgroup than it was in the control (PBS) subgroup at 1-3 weeks (P < 0.001). Immunofluorescence staining for S100 showed the continuity of nerve fibers recovered more quickly in the EA+BMSCs subgroup than in the BMSCs subgroup. Conclusion: Our research revealed that a combination of MSCs and EA can provide both topological and biomolecular guidance to promote axonal extension, myelin regeneration, and functional recovery after PNI. EA not only promotes nerve repair on its own, but also enhanced the beneficial effects of stem cell treatment and the secretion of netrin 1, a guidance regeneration factor, and promotes the orderly growth of nerve fibers. These PNI repairs could be monitored non-invasively and in situ by MRI. The FA and RD values derived from MRI could be sensitive biomarkers to reflect the PNI repair process.
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Affiliation(s)
- Yueyao Chen
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Zhongxian Pan
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Fanqi Meng
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Xuewen Yu
- Department of Pathology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Qian Xu
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Leyu Huang
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | - Qiumei Liang
- Department of Radiology, Shenzhen Traditional Chinese Medicine Hospital (The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine), Shenzhen, China
| | | | - Xiaofeng Lin
- Department of Nuclear Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China,*Correspondence: Xiaofeng Lin
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Yuan ZQ, Yan HL, Li JW, Luo Y. Contrast-enhanced ultrasound of a traumatic neuroma of the extrahepatic bile duct: A case report and review of literature. World J Gastroenterol 2022; 28:4211-4220. [PMID: 36157104 PMCID: PMC9403427 DOI: 10.3748/wjg.v28.i30.4211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 04/17/2022] [Accepted: 07/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Traumatic neuromas result from nerve injury after trauma or surgery but rarely occur in the bile duct. However, it is challenging to diagnose traumatic neuromas correctly preoperatively. Although some previous reports have described the imaging features of traumatic neuroma in the bile duct, no features of traumatic neuromas in the bile duct have been identified by using contrast-enhanced ultrasound (CEUS) imaging before.
CASE SUMMARY A 55-year-old male patient presented to our hospital with a 3-mo history of abdominal distension and anorexia and history of cholecystectomy 4 years ago. Grayscale ultrasound demonstrated mild to moderate intrahepatic bile duct dilatation. Meanwhile, a hyperechoic nodule was found in the upper extrahepatic bile duct. The lesion approximately 0.8 cm × 0.6 cm with a regular shape and clear margins. The nodule of the bile duct showed slight hyperenhancement in the arterial phase and isoenhancement in the venous phase on CEUS. Laboratory tests showed that alanine aminotransferase and aspartate aminotransferase were increased significantly, while the tumor marker carbohydrate antigen 19-9 was increased slightly. Then, hilar bile duct resection and end-to-end bile ductal anastomosis were performed. The histological examination revealed traumatic neuroma of the extrahepatic bile duct. The patient had an uneventful recovery after surgery.
CONCLUSION The current report will help enhance the current knowledge regarding identifying traumatic neuromas by CEUS imaging and review the related literature.
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Affiliation(s)
- Zhi-Qiang Yuan
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hua-Lin Yan
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Wu Li
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Luo
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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Chung BM, Lee GY, Kim WT, Kim I, Lee Y, Park SB. MRI features of symptomatic amputation neuromas. Eur Radiol 2021; 31:7684-7695. [PMID: 33866387 DOI: 10.1007/s00330-021-07954-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/13/2021] [Accepted: 03/26/2021] [Indexed: 01/15/2023]
Abstract
OBJECTIVES To demonstrate the magnetic resonance imaging (MRI) features of amputation neuromas in lower extremity amputees and investigate independent predictive MRI features for symptomatic neuromas. METHODS This retrospective study included 45 amputation neuromas in 44 lower extremity amputees. Two radiologists assessed the imaging features, including shape, size, type (end-bulb or spindle), signal intensity (SI), heterogeneity, margins, enlarged fascicles, dark outer rim, tail sign, target sign, enhancement, perilesional fibrosis, and muscle denervation. The neuromas were categorized into symptomatic (n = 24) or asymptomatic (n = 21). Symptomatic neuromas were determined based on neuropathic pain characteristics, the presence of Tinel's sign or tenderness, and response to local anesthetic injection. Univariate and multivariate analyses were performed to identify independent predictive MRI features. RESULTS Of 45 neuromas, 80% (36/45) were end-bulb neuromas and 20% (9/45) were spindle-type neuromas. Eighty percent of the neuromas (36/45) were heterogeneous on T2-weighted images (WIs). Enlarged fascicles were present in 42% (19/45) and dark outer rims in 27% (12/45) of the neuromas. Among the 23 neuromas with enhanced images, 78% (18/23) showed enhancement. Heterogeneity on T2-WIs and enhancement ratios were significantly different between the asymptomatic and symptomatic neuroma groups (p < 0.05). The multivariate analyses indicated that heterogeneity on T2-WIs was an independent factor associated with symptomatic neuromas (p < 0.001). CONCLUSIONS Heterogeneity on T2-WIs could be a predictive indicator for symptomatic neuromas in lower extremity amputees. KEY POINTS • Amputation neuromas are classified as either end-bulb or spindle-type. They can show enlarged fascicles, dark outer rims, and enhancement. • Heterogeneity on T2-weighted images could be a predictive indicator for symptomatic neuromas. • Predicting the symptomatic neuroma on MRI would help in effective management of stump pain.
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Affiliation(s)
- Bo Mi Chung
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102, Heukseok-ro, Dongjak-Gu, Seoul, 156-755, Republic of Korea
- Department of Radiology, Veterans Health Service Medical Center, 53, Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul, 05368, Republic of Korea
| | - Guen Young Lee
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102, Heukseok-ro, Dongjak-Gu, Seoul, 156-755, Republic of Korea
| | - Wan Tae Kim
- Department of Radiology, Veterans Health Service Medical Center, 53, Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul, 05368, Republic of Korea
| | - Injoong Kim
- Department of Radiology, Veterans Health Service Medical Center, 53, Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul, 05368, Republic of Korea
| | - Young Lee
- Veterans Medical Research Institute, Veterans Health Service Medical Center, 53, Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul, 05368, Republic of Korea
| | - Sung Bin Park
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102, Heukseok-ro, Dongjak-Gu, Seoul, 156-755, Republic of Korea.
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Zheng C, Yang Z, Chen S, Zhang F, Rao Z, Zhao C, Quan D, Bai Y, Shen J. Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair. Theranostics 2021; 11:2917-2931. [PMID: 33456580 PMCID: PMC7806490 DOI: 10.7150/thno.50825] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022] Open
Abstract
Rationale: Peripheral nerve injury (PNI) is a great challenge for regenerative medicine. Nerve autograft is the gold standard for clinical PNI repair. Due to its significant drawbacks, artificial nerve guidance conduits (NGCs) have drawn much attention as replacement therapies. We developed a combinatorial NGC consisting of longitudinally aligned electrospun nanofibers and porcine decellularized nerve matrix hydrogel (pDNM gel). The in vivo capacity for facilitating nerve tissue regeneration and functional recovery was evaluated in a rat sciatic nerve defect model. Methods: Poly (L-lactic acid) (PLLA) was electrospun into randomly oriented (PLLA-random) and longitudinally aligned (PLLA-aligned) nanofibers. PLLA-aligned were further coated with pDNM gel at concentrations of 0.25% (PLLA-aligned/0.25% pDNM gel) and 1% (PLLA-aligned/1% pDNM gel). Axonal extension and Schwann cells migration were evaluated by immunofluorescence staining of dorsal root ganglia cultured on the scaffolds. To fabricate implantable NGCs, the nanofibrous scaffolds were rolled and covered with an electrospun protection tube. The fabricated NGCs were then implanted into a 5 mm sciatic nerve defect model in adult male Sprague-Dawley rats. Nerves treated with NGCs were compared to contralateral uninjured nerves (control group), injured but untreated nerves (unstitched group), and autografted nerves. Nerve regeneration was monitored by an established set of assays, including T2 values and diffusion tensor imaging (DTI) derived from multiparametric magnetic resonance imaging (MRI), histological assessments, and immunostaining. Nerve functional recovery was evaluated by walking track analysis. Results: PLLA-aligned/0.25% pDNM gel scaffold exhibited the best performance in facilitating directed axonal extension and Schwann cells migration in vitro due to the combined effects of the topological cues provided by the aligned nanofibers and the biochemical cues retained in the pDNM gel. Consistent results were obtained in animal experiments with the fabricated NGCs. Both the T2 and fractional anisotropy values of the PLLA-aligned/0.25% pDNM gel group were the closest to those of the autografted group, and returned to normal much faster than those of the other NGCs groups. Histological assessment indicated that the implanted PLLA-aligned/0.25% pDNM gel NGC resulted in the largest number of axons and the most extensive myelination among all fabricated NGCs. Further, the PLLA-aligned/0.25% pDNM gel group exhibited the highest sciatic nerve function index, which was comparable to that of the autografted group, at 8 weeks post-surgery. Conclusions: NGCs composed of aligned PLLA nanofibers decorated with 0.25% pDNM gel provided both topological and biochemical guidance for directing and promoting axonal extension, nerve fiber myelination, and functional recovery. Moreover, T2-mapping and DTI metrics were found to be useful non-invasive monitoring techniques for PNI treatment.
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Affiliation(s)
- Chushan Zheng
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
| | - Zehong Yang
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
| | - Shihao Chen
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Fang Zhang
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
| | - Zilong Rao
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Cailing Zhao
- Guangdong Functional Biomaterials Engineering Technology Research Center, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Daping Quan
- PCFM Lab, GD HPPC Lab, School of Chemistry, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
- Guangdong Functional Biomaterials Engineering Technology Research Center, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Ying Bai
- Guangdong Functional Biomaterials Engineering Technology Research Center, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
| | - Jun Shen
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, China
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Muratori L, Fregnan F, Ronchi G, Haastert-Talini K, Metzen J, Bertolo R, Porpiglia F, Geuna S. New basic insights on the potential of a chitosan-based medical device for improving functional recovery after radical prostatectomy. BJU Int 2019; 124:1063-1076. [PMID: 31134718 DOI: 10.1111/bju.14834] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To evaluate: (i) the neuro-regenerative potential of chitosan membrane (CS-Me) on acutely axotomised autonomic neurones in vitro; (ii) to exclude the possibility that a pro-regenerative biomaterial could interfere with the proliferation activity of prostate cancer cell lines; (iii) to provide an in vivo proof of the biocompatibility and regeneration promoting effect of CS-Me in a standardised rat model of peripheral nerve injury and repair; (iv) finally, to evaluate the tissue reaction induced by the degrading material; as previous studies have shown promising effects of CS-Me for protection of the neurovascular bundles for potency recovery in patients that undergo nerve-sparing radical prostatectomy (RP). MATERIALS AND METHODS Addressing aim (i), the neuro-regenerative potential, organotypic cultures derived from primary sympathetic ganglia were cultured on CS-Me over 3 days and neurite extension and axonal sprouting were evaluated. Addressing aim (ii), effects of CS on cancer cells, different human prostate cancer cell lines (PC3, DU-145, LN-Cap) were seeded on CS-coated plates or cultured in the presence of CS-Me dissolution products. Addressing aims (iii) and (iv), functional recovery of peripheral nerve fibres and tissue reaction with the biomaterial, CS-Me and CS nerve guides were used to repair a median nerve injury in the rat. Functional recovery was evaluated during the post-recovery time by the behavioural grasping test. RESULTS CS-Me significantly stimulated axon elongation from autonomic ganglia in comparison to control conditions in organotypic three-dimensional cultures. CS coating, as well as the dissolution products of CS-Me, led to a significantly lower proliferation rate of prostate cancer cell lines in vitro. Tissue reaction towards CS-Me and standard CS nerve guides was similar in the rat median nerve model, as was the outcome of nerve fibre regeneration and functional recovery. CONCLUSION The results of this study provide the first experimental evidence in support of the clinical safety of CS-Me and of their postulated effectiveness for improving functional recovery after RP. The presented results are coherent in demonstrating that acutely axotomised autonomic neurones show increased neurite outgrowth on CS-Me substrate, whilst the same substrate reduces prostate cancer cell line proliferation in vitro. Furthermore, CS-Me do not demonstrate any disadvantage for peripheral nerve repair in a standard animal model.
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Affiliation(s)
- Luisa Muratori
- Department of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Orbassano, Italy
| | - Federica Fregnan
- Department of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Orbassano, Italy
| | - Giulia Ronchi
- Department of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Orbassano, Italy
| | - Kirsten Haastert-Talini
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Center for Systems Neuroscience (ZSN), Hannover, Germany
| | - Jennifer Metzen
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Hannover, Germany
| | - Riccardo Bertolo
- Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Francesco Porpiglia
- Division of Urology, Department of Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy
- Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy
| | - Stefano Geuna
- Department of Clinical and Biological Sciences, Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Orbassano, Italy
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Cohen E, Merzendorfer H. Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications. EXTRACELLULAR SUGAR-BASED BIOPOLYMERS MATRICES 2019; 12. [PMCID: PMC7115017 DOI: 10.1007/978-3-030-12919-4_14] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Chitin is a linear polysaccharide of N-acetylglucosamine, which is highly abundant in nature and mainly produced by marine crustaceans. Chitosan is obtained by hydrolytic deacetylation. Both polysaccharides are renewable resources, simply and cost-effectively extracted from waste material of fish industry, mainly crab and shrimp shells. Research over the past five decades has revealed that chitosan, in particular, possesses unique and useful characteristics such as chemical versatility, polyelectrolyte properties, gel- and film-forming ability, high adsorption capacity, antimicrobial and antioxidative properties, low toxicity, and biocompatibility and biodegradability features. A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. The number of studies in this research field has exploded particularly during the last two decades. Here, we review recent advances in utilizing chitosan and chitosan derivatives in different technical, agricultural, and biomedical fields.
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Affiliation(s)
- Ephraim Cohen
- Department of Entomology, The Robert H. Smith Faculty of Agriculture Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel
| | - Hans Merzendorfer
- School of Science and Technology, Institute of Biology – Molecular Biology, University of Siegen, Siegen, Germany
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Wang D, Wang C, Duan X, Yang Z, Bai Z, Hu H, Yan L, Shen J. MR T2 value of the tibial nerve can be used as a potential non-invasive and quantitative biomarker for the diagnosis of diabetic peripheral neuropathy. Eur Radiol 2018; 28:1234-1241. [PMID: 29038932 DOI: 10.1007/s00330-017-5043-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 08/14/2017] [Accepted: 08/18/2017] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To determine the role of quantitative tibial nerve T2 value in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS MR imaging and T2 mapping of the tibial nerve were performed in 22 diabetic patients with DPN, 20 diabetic patients without DPN and 20 healthy controls. Nerve T2 values were measured, and compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic ability of T2 value to identify DPN. RESULTS Nerve T2 value was 55.06 ± 4.05 ms, 48.91 ± 3.06 ms and 45.61 ± 1.86 ms in patients with DPN, patients without DPN and controls, respectively. Patients with DPN had significantly higher nerve T2 values than patients without DPN (P < 0.001). Nerve T2 values in patients without DPN were higher than in controls (P < 0.001). ROC analysis showed that T2 values had a diagnostic sensitivity of 81.8 %, specificity of 89.2 % and area under the curve of 0.922 for identifying patients with DPN from patients without DPN plus controls when the cutoff point was 51.34 ms. CONCLUSION T2 value of the tibial nerve can be used as an alternative, non-invasive quantitative parameter to assess DPN in diabetic patients. KEY POINTS • Tibial nerves in patients with DPN showed T2 hyperintensity and enlargement. • Tibial nerves in patients with DPN had an increased T2 value. • T2 value might be used as a quantitative biomarker for DPN.
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Affiliation(s)
- Dongye Wang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China
| | - Chuan Wang
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China
| | - Xiaohui Duan
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China
| | - Zehong Yang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China
| | - Zhiqiang Bai
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China
| | - Huijun Hu
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China
| | - Li Yan
- Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China.
| | - Jun Shen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 510120, China.
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Chen MW, Zhang X, Lu LJ, Zhang F, Duan XH, Zheng CS, Chen YY, Shen J. Monitoring of macrophage recruitment enhanced by Toll-like receptor 4 activation with MR imaging in nerve injury. Muscle Nerve 2018; 58:123-132. [PMID: 29424947 DOI: 10.1002/mus.26097] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2018] [Indexed: 01/23/2023]
Abstract
INTRODUCTION Macrophage recruitment is critical for nerve regeneration after an injury. The aim of this study was to investigate whether ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle-based MRI could be used to monitor the enhanced macrophage recruitment by Toll-like receptor 4 (TLR4) activation in nerve injury. METHODS Rats received intraperitoneal injections of either lipopolysaccharide (LPS) or phosphate buffered saline (PBS) or no injection (controls) after a sciatic nerve crush injury. After intravenous injection of the USPIOs (LPS and PBS groups) or PBS (control group), MRI was performed and correlated with histological findings. RESULTS LPS group showed more remarkable hypointense signals on T2*-weighted imaging and lower T2 values in the crushed nerves than PBS group. The hypointense signal areas were associated with an enhanced recruitment of iron-loaded macrophages to the injured nerves. DISCUSSION USPIO-enhanced MRI can be used to monitor the enhanced macrophage recruitment by means of TLR4 signal pathway activation in nerve injury. Muscle Nerve, 2018.
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Affiliation(s)
- Mei-Wei Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Xiang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Lie-Jing Lu
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Fang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Xiao-Hui Duan
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Chu-Shan Zheng
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Yue-Yao Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
| | - Jun Shen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No.107 Yanjiang Road West, Guangzhou, 510120, China
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Zheng CS, Zhang X, Chen YY, Zhang F, Duan XH, Chen MW, Lu LJ, Shen J. Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging. Muscle Nerve 2018; 57:E38-E45. [PMID: 28445921 DOI: 10.1002/mus.25674] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 04/05/2017] [Accepted: 04/23/2017] [Indexed: 01/15/2023]
Abstract
INTRODUCTION The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis. METHODS Rats with sciatic nerve neurotmesis and surgical repair underwent serial multiparametric MR examinations over an 8-week period after subepineurial microinjection of lipopolysaccharide (LPS) and subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS or phosphate-buffered saline (PBS) alone. RESULTS Nerves treated with immunomodulation showed more prominent regeneration than those treated with LPS or PBS alone and more rapid restoration toward normal T2, fractional anisotropy (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS. DISCUSSION Nerves treated with immunomodulation exert synergic beneficial effects on nerve regeneration that can be predicted by T2 measurements and FA and RD values. Muscle Nerve 57: E38-E45, 2018.
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Affiliation(s)
- Chu-Shan Zheng
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Xiang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Yue-Yao Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Fang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Xiao-Hui Duan
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Mei-Wei Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Lie-Jing Lu
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
| | - Jun Shen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
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12
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Yao Z, Yan LW, Wang T, Qiu S, Lin T, He FL, Yuan RH, Liu XL, Qi J, Zhu QT. A rapid micro-magnetic resonance imaging scanning for three-dimensional reconstruction of peripheral nerve fascicles. Neural Regen Res 2018; 13:1953-1960. [PMID: 30233069 PMCID: PMC6183031 DOI: 10.4103/1673-5374.238718] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The most common methods for three-dimensional reconstruction of peripheral nerve fascicles include histological and radiology techniques. Histological techniques have many drawbacks including an enormous manual workload and poor image registration. Micro-magnetic resonance imaging (Micro-MRI), an emerging radiology technique, has been used to report results in the brain, liver and tumor tissues. However, micro-MRI usage for obtaining intraneural structures has not been reported. The aim of this study was to present a new imaging method for three-dimensional reconstruction of peripheral nerve fascicles by 1T micro-MRI. Freshly harvested sciatic nerve samples from an amputated limb were divided into four groups. Two different scanning conditions (Mannerist Solution/GD-DTPA contrast agent, distilled water) were selected, and both T1 and T2 phases programmed for each scanning condition. Three clinical surgeons evaluated the quality of the images via a standardized scale. Moreover, to analyze deformation of the two-dimensional image, the nerve diameter and total area of the micro-MRI images were compared after hematoxylin-eosin staining. The results show that rapid micro-MRI imaging method can be used for three-dimensional reconstruction of the fascicle structure. Nerve sample immersed in contrast agent (Mannerist Solution/GD-DTPA) and scanned in the T1 phase was the best. Moreover, the nerve sample was scanned freshly and can be recycled for other procedures. MRI images show better stability and smaller deformation compared with histological images. In conclusion, micro-MRI provides a feasible and rapid method for three-dimensional reconstruction of peripheral nerve fascicles, which can clearly show the internal structure of the peripheral nerve.
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Affiliation(s)
- Zhi Yao
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Li-Wei Yan
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Tao Wang
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Shuai Qiu
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Tao Lin
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Fu-Lin He
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Ru-Heng Yuan
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Xiao-Lin Liu
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research; Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China
| | - Jian Qi
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research; Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China
| | - Qing-Tang Zhu
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research; Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China
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Hill BJ, Padgett KR, Kalra V, Marcillo A, Bowen B, Pattany P, Dietrich D, Quencer R. Gadolinium DTPA Enhancement Characteristics of the Rat Sciatic Nerve after Crush Injury at 4.7T. AJNR Am J Neuroradiol 2017; 39:177-183. [PMID: 29097415 DOI: 10.3174/ajnr.a5437] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 08/24/2017] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.
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Affiliation(s)
- B J Hill
- From the Departments of Radiology (B.J.H., K.R.P., B.B., P.P., R.Q.)
| | - K R Padgett
- From the Departments of Radiology (B.J.H., K.R.P., B.B., P.P., R.Q.) .,Radiation Oncology (K.R.P.).,Biomedical Engineering (K.R.P.)
| | - V Kalra
- Miller School of Medicine (V.K.), University of Miami, Miami, Florida
| | - A Marcillo
- Miami Project to Cure Paralysis (A.M., D.D.)
| | - B Bowen
- From the Departments of Radiology (B.J.H., K.R.P., B.B., P.P., R.Q.)
| | - P Pattany
- From the Departments of Radiology (B.J.H., K.R.P., B.B., P.P., R.Q.)
| | - D Dietrich
- Miami Project to Cure Paralysis (A.M., D.D.)
| | - R Quencer
- From the Departments of Radiology (B.J.H., K.R.P., B.B., P.P., R.Q.)
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Yang Q, Xia D, Towner RA, Smith N, Saunders D, Fung KM, Aston CE, Greenwood-Van Meerveld B, Hurst RE, Madihally SV, Kropp BP, Lin HK. Reduced urothelial regeneration in rat bladders augmented with permeable porcine small intestinal submucosa assessed by magnetic resonance imaging. J Biomed Mater Res B Appl Biomater 2017; 106:1778-1787. [DOI: 10.1002/jbm.b.33985] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 08/02/2017] [Accepted: 08/16/2017] [Indexed: 12/28/2022]
Affiliation(s)
- Qing Yang
- Department of Urology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
| | - Ding Xia
- Department of Urology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
- Department of Urology; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Wuhan Hubei 430030 People's Republic of China
| | - Rheal A. Towner
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation; Oklahoma City Oklahoma 73104
- Oklahoma Center for Neuroscience; Oklahoma City Oklahoma 73104
- Department of Pathology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
| | - Nataliya Smith
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation; Oklahoma City Oklahoma 73104
| | - Debra Saunders
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation; Oklahoma City Oklahoma 73104
| | - Kar-Ming Fung
- Department of Urology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
- Oklahoma Center for Neuroscience; Oklahoma City Oklahoma 73104
- Oklahoma City Department of Veterans Affairs Medical Center; Oklahoma City Oklahoma 73104
| | - Christopher E. Aston
- Department of Pediatrics; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
| | - Beverley Greenwood-Van Meerveld
- Oklahoma Center for Neuroscience; Oklahoma City Oklahoma 73104
- Department of Physiology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
| | - Robert E. Hurst
- Department of Urology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
- Department of Biochemistry and Molecular Biology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
| | | | - Bradley P. Kropp
- Department of Urology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
| | - Hsueh-Kung Lin
- Department of Urology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
- Oklahoma Center for Neuroscience; Oklahoma City Oklahoma 73104
- Department of Physiology; University of Oklahoma Health Sciences Center; Oklahoma City Oklahoma 73104
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15
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Versatility of Chitosan-Based Biomaterials and Their Use as Scaffolds for Tissue Regeneration. ScientificWorldJournal 2017; 2017:8639898. [PMID: 28567441 PMCID: PMC5439263 DOI: 10.1155/2017/8639898] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 03/10/2017] [Accepted: 04/03/2017] [Indexed: 01/05/2023] Open
Abstract
Chitosan is a naturally occurring polysaccharide obtained from chitin, present in abundance in the exoskeletons of crustaceans and insects. It has aroused great interest as a biomaterial for tissue engineering on account of its biocompatibility and biodegradation and its affinity for biomolecules. A significant number of research groups have investigated the application of chitosan as scaffolds for tissue regeneration. However, there is a wide variability in terms of physicochemical characteristics of chitosan used in some studies and its combinations with other biomaterials, making it difficult to compare results and standardize its properties. The current systematic review of literature on the use of chitosan for tissue regeneration consisted of a study of 478 articles in the PubMed database, which resulted, after applying inclusion criteria, in the selection of 61 catalogued, critically analysed works. The results demonstrated the effectiveness of chitosan-based biomaterials in 93.4% of the studies reviewed, whether or not combined with cells and growth factors, in the regeneration of various types of tissues in animals. However, the absence of clinical studies in humans, the inadequate experimental designs, and the lack of information concerning chitosan's characteristics limit the reproducibility and relevance of studies and the clinical applicability of chitosan.
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Mitchell CH, Fayad LM, Ahlawat S. Magnetic Resonance Imaging of the Digital Nerves of the Hand: Anatomy and Spectrum of Pathology. Curr Probl Diagn Radiol 2017; 47:42-50. [PMID: 28438411 DOI: 10.1067/j.cpradiol.2017.02.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 02/28/2017] [Accepted: 02/28/2017] [Indexed: 01/20/2023]
Abstract
Digital nerves are intrinsic to the sensory and motor function of the hand. These nerves represent the terminal ramifications of the ulnar, median, and radial nerves and are located distal to the carpal tunnel and Guyon canal. With magnetic resonance imaging, traumatic and nontraumatic abnormalities of the digital nerves can be shown with high contrast as well as high spatial resolution. Digital nerve abnormalities are most commonly posttraumatic in nature; however, infection, inflammatory, vascular malformations, and neoplasms can rarely occur. Magnetic resonance imaging is playing an increasing role in the assessment of peripheral nerve injury throughout the body, and in the hand, which can accurately identify the extent and character of digital nerve abnormalities before operative intervention.
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Affiliation(s)
- Charles H Mitchell
- The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Laura M Fayad
- The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD
| | - Shivani Ahlawat
- The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, MD.
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17
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Chen YY, Zhang X, Lin XF, Zhang F, Duan XH, Zheng CS, Chen MW, Wang DY, Zeng WK, Shen J. DTI metrics can be used as biomarkers to determine the therapeutic effect of stem cells in acute peripheral nerve injury. J Magn Reson Imaging 2017; 45:855-862. [PMID: 27448779 DOI: 10.1002/jmri.25395] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 07/05/2016] [Indexed: 12/20/2022] Open
Abstract
PURPOSE To determine the role of diffusion tensor imaging (DTI) metrics as biomarkers for the therapeutic effects of mesenchymal stem cells (MSCs) in acute peripheral nerve injury. MATERIALS AND METHODS Forty-four adult rats received subepineurial microinjection of MSCs (n = 22) or phosphate buffered saline (PBS, n = 22) 1 week after the sciatic nerve trunk crush injury. Sequential fat-suppressed T2-weighted imaging, T2 measurement, DTI and sciatic nerve functional assessment were performed at a 3.0 Tesla MR unit over an 8-week follow-up, with histological assessments performed at regular intervals. The sciatic nerve function index, T2 value, and DTI metrics, including fractional anisotropy (FA), axial diffusivity, radial diffusivity (RD), and mean diffusivity values of the distal stumps of crushed nerves were measured and compared between the two groups. RESULTS Nerves treated with MSCs showed better functional recovery and exhibited more pronounced nerve regeneration compared with nerves treated with PBS. T2 values in nerves treated with MSCs or PBS showed a similar change pattern (P = 0.174), while FA and RD values in nerves treated with MSCs showed more rapid return (one week earlier) to baseline level than nerves treated with PBS (P = 0.045; 0.035). Nerves treated with MSCs had higher FA and lower RD values than nerves treated with PBS during the period from 2 to 3 weeks after surgery (P ≤ 0.0001, 0.004; P = 0.004, 0.006). CONCLUSION FA and RD values derived from DTI might be used as sensitive biomarkers for detecting the therapeutic effect of stem cells in acute peripheral nerve crush injuries. LEVEL OF EVIDENCE 2 J. Magn. Reson. Imaging 2017;45:855-862.
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Affiliation(s)
- Yue-Yao Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiao-Feng Lin
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Fang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiao-Hui Duan
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Chu-Shan Zheng
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Mei-Wei Chen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Dong-Ye Wang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wei-Ke Zeng
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jun Shen
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
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Semiquantitative assessment of optic nerve injury using manganese-enhanced MRI. Jpn J Radiol 2016; 34:356-65. [PMID: 26943911 DOI: 10.1007/s11604-016-0533-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Accepted: 02/22/2016] [Indexed: 10/22/2022]
Abstract
OBJECTIVE To evaluate the capability of manganese (Mn(2+))-enhanced MRI (MEMRI) in a continuously semiquantitative assessment of rat optic nerve (ON) injury. METHODS Forty rats were divided into three groups: (I) a control group that was submitted to MEMRI or to fluorescent labeling of retinal ganglion cells (RGCs) (n = 10); (II) an ON injury group that was submitted to MEMRI (n = 15); (III) an ON injury group that was submitted to fluorescent labeling of RGCs (n = 15). Groups II and III were examined at 3, 7, and 14 days post-lesion (dpl), when the contrast-to-noise ratio (CNR) of the retina and ON was measured on MEMRI images and the RGCs were counted by fluorescence microscopy and compared between the groups. RESULTS In the control group, the intact visual pathway from the retina to the contralateral superior colliculus was visualized by MEMRI. In group II, continuous Mn(2+) enhancement was seen from the retina to the lesion site of the optic nerves at 3, 7, and 14 dpl. However, no Mn(2+) enhancement was observed distal to the lesion site at those time points. The observed Mn(2+) enhancement proximal to the ON lesion site declined between 7 and 14 dpl. The decrease in Mn(2+)-enhanced signal intensity at these sites at 7 and 14 dpl when compared to that at 3 dpl was significant (P < 0.05). The RGC density dropped by 6.84, 45.31, and 72.36 % at 3, 7, and 14 dpl, respectively. CONCLUSION MEMRI can be used to evaluate the structural changes after optic nerve injury.
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Tissue-engineered conduit promotes sciatic nerve regeneration following radiation-induced injury as monitored by magnetic resonance imaging. Magn Reson Imaging 2015; 34:515-23. [PMID: 26686023 DOI: 10.1016/j.mri.2015.12.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 12/03/2015] [Accepted: 12/07/2015] [Indexed: 12/17/2022]
Abstract
PURPOSE To observe the longitudinal changes in peripheral nerve repaired with chitosan conduits in a rat model of radiation-induced neuropathy. MATERIALS AND METHODS Four months after 40 Gy radiation to the right lower limbs, forty-two rats were divided randomly into three groups. Chitosan conduits were implanted with (group A, n=12) or without (group B, n=12) mesenchymal stem cells (MSCs), and untreated controls (group C, n=12). Following sciatic nerve MR imaging (including T2WI and Gd-DTPA enhanced T1WI), functional evaluation and electrophysiological exam were performed two-monthly, final histological assessments were done at the end of one year. The differences among the experimental and control groups were statistically analysed with Fisher's PLSD or t-test. RESULTS The compound muscle action potentials (CMAPs) and sciatic function index (SFI) had declined since 4 months after radiation injury. The focal nerve enlargement and hyperintensity, the perineurium and connecting muscle enhancement were demonstrated by MR neurography images. After chitosan tube implantation, the normalized signal intensities (SIs) in group A were declined more rapidly than SIs in other groups. The histological assessments indicated that group A had better remyelination, combined with higher CMAPs amplitude and SFI score than other groups. CONCLUSION A single fraction dose of 40 Gy can be used to establish a rat model of sciatic nerve injury. Longitudinal electrophysiological examination and MR neurography are useful to evaluate the post-irradiation sciatic neuropathy. The rats with tissue-engineered conduits implantation showed some improvement of lower limb function, accompanied by a normalization of (T1W/T2W) MR signal.
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Ahlawat S, Belzberg AJ, Montgomery EA, Fayad LM. MRI features of peripheral traumatic neuromas. Eur Radiol 2015; 26:1204-12. [PMID: 26188658 DOI: 10.1007/s00330-015-3907-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 05/06/2015] [Accepted: 06/29/2015] [Indexed: 12/23/2022]
Abstract
OBJECTIVES To describe the MRI appearance of traumatic neuromas on non-contrast and contrast-enhanced MRI sequences. METHODS This IRB-approved, HIPAA-compliant study retrospectively reviewed 13 subjects with 20 neuromas. Two observers reviewed pre-operative MRIs for imaging features of neuroma (size, margin, capsule, signal intensity, heterogeneity, enhancement, neurogenic features and denervation) and the nerve segment distal to the traumatic neuroma. Descriptive statistics were reported. Pearson's correlation was used to examine the relationship between size of neuroma and parent nerve. RESULTS Of 20 neuromas, 13 were neuromas-in-continuity and seven were end-bulb neuromas. Neuromas had a mean size of 1.5 cm (range 0.6-4.8 cm), 100 % (20/20) had indistinct margins and 0 % (0/20) had a capsule. Eighty-eight percent (7/8) showed enhancement. All 100 % (20/20) had tail sign; 35 % (7/20) demonstrated discontinuity from the parent nerve. None showed a target sign. There was moderate positive correlation (r = 0.68, p = 0.001) with larger neuromas arising from larger parent nerves. MRI evaluation of the nerve segment distal to the neuroma showed increased size (mean size 0.5 cm ± 0.4 cm) compared to the parent nerve (mean size 0.3 cm ± 0.2 cm). CONCLUSION Since MRI features of neuromas include enhancement, intravenous contrast medium cannot be used to distinguish neuromas from peripheral nerve sheath tumours. The clinical history of trauma with the lack of a target sign are likely the most useful clues. KEY POINTS • MRI features of neuromas include enhancement and lack of a target sign. • Contrast material cannot be used to distinguish traumatic neuromas from PNSTs. • Traumatic neuromas can simulate peripheral nerve neoplasms on imaging.
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Affiliation(s)
- Shivani Ahlawat
- Musculoskeletal Radiology Section, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 North Wolfe Street, Baltimore, MD, 21287, USA.
| | - Allan J Belzberg
- Department of Neurosurgery, The Johns Hopkins Hospital, Meyer Bldg, Room 5-181, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
| | - Elizabeth A Montgomery
- Pathology, Oncology and Orthopedic Surgery, The Johns Hopkins Hospital, Weinberg Room 2242, 600 N. Wolfe Street, Sheikh Zayed Tower, Baltimore, MD, 21287, USA.
| | - Laura M Fayad
- Department of Radiology and Radiological Science, Musculoskeletal Imaging Section Chief, Department of Orthopedic Surgery, The Johns Hopkins Medical Institutions, 601 North Wolfe Street, Baltimore, MD, 21287, USA. .,Department of Orthopedic Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD, 21287, USA.
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Sarabia-Estrada R, Bañuelos-Pineda J, Osuna Carrasco LP, Jiménez-Vallejo S, Jiménez-Estrada I, Rivas-Celis E, Dueñas-Jiménez JM, Dueñas-Jiménez SH. Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve. J Neurosurg 2015; 123:270-82. [DOI: 10.3171/2014.12.jns132519] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECT
Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats.
METHODS
After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection.
RESULTS
At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes. Some gastrocnemius efferent fibers were partially repaired 90 days after nerve resection. The better outcome in knee angle displacement may be partially attributable to the aberrant neuromuscular synaptic effects, since nerve conduction in the gastrocnemius muscle could be blocked in the progesterone-impregnated chitosan tubes. In addition, in the region of the gap produced by the nerve resection, the number of axons and amount of myelination were reduced in the sciatic nerve implanted with chitosan, progesterone-loaded chitosan, and silicone tubes. At 180 days after sciatic nerve sectioning, the knee kinematic function recovered to a level observed in control rats of a similar age. In rats with progesterone-loaded chitosan tubes, stimulation of the proximal and intratubular sciatic nerve segments produced an electromyographic response. The axon morphology of the proximal and intratubular segments of the sciatic nerve resembled that of the contralateral nontransected nerve.
CONCLUSIONS
Progesterone-impregnated chitosan tubes produced aberrant innervation of the gastrocnemius muscle, which allowed partial recovery of gait locomotion and could be adequate for reinnervating synergistic denervated muscles while a parent innervation is reestablished. Hindlimb kinematic parameters differed between younger (those at 90 days) and older (those at 180 days) rats.
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Affiliation(s)
| | | | | | | | - Ismael Jiménez-Estrada
- 3Department of Physiology, Biophysics and Neurosciences, CINVESTAV, IPN, México City D.F., México
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Wang D, Zhang X, Lu L, Li H, Zhang F, Chen Y, Shen J. Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging. Eur Radiol 2015; 25:463-471. [PMID: 25204416 DOI: 10.1007/s00330-014-3423-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2014] [Revised: 08/12/2014] [Accepted: 08/28/2014] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). METHODS Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7 weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. RESULTS Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2 weeks after the induction (P = 0.014), while a decrease in MWT started at 3 weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3 weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. CONCLUSION Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. KEY POINTS • Sciatic nerves in diabetic rats showed a gradual increase in T2 values • Nerve T2 values were negatively correlated with sensory function impairment • Longitudinal T2 values can be used to monitor the disease progress • Nerve degeneration contributed mainly to progressive prolongation of nerve T2 values.
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Affiliation(s)
- Dongye Wang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, Guangdong, 51012, China
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23
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Geuna S. The sciatic nerve injury model in pre-clinical research. J Neurosci Methods 2015; 243:39-46. [PMID: 25629799 DOI: 10.1016/j.jneumeth.2015.01.021] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 01/15/2015] [Accepted: 01/16/2015] [Indexed: 12/15/2022]
Abstract
In the pre-clinical view, the study of peripheral nerve repair and regeneration still needs to be carried out in animal models due to the structural complexity of this organ which can be only partly simulated in vitro. The far most used experimental model is based on the injury of the sciatic nerve, the largest nerve trunk in mammals. In this paper, the potential application of the sciatic nerve injury model in pre-clinical research is critically reviewed. This paper is aimed at helping researchers in properly employing this in vivo model for the study of nerve repair and regeneration as well as interpreting the results in a clinical translation perspective.
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Affiliation(s)
- Stefano Geuna
- Neuroscience Institute of the Cavalieri Ottolenghi Foundation & Department of Clinical and Biological Sciences, University of Turin, Italy.
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24
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3D multi-channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration. J Mech Behav Biomed Mater 2015; 41:43-55. [DOI: 10.1016/j.jmbbm.2014.09.029] [Citation(s) in RCA: 139] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 09/25/2014] [Accepted: 09/30/2014] [Indexed: 12/21/2022]
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26
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Dinis TM, Elia R, Vidal G, Auffret A, Kaplan DL, Egles C. Method to form a fiber/growth factor dual-gradient along electrospun silk for nerve regeneration. ACS APPLIED MATERIALS & INTERFACES 2014; 6:16817-16826. [PMID: 25203247 DOI: 10.1021/am504159j] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Concentration gradients of guidance molecules influence cell behavior and growth in biological tissues and are therefore of interest for the design of biomedical scaffolds for regenerative medicine. We developed an electrospining method to generate a dual-gradient of bioactive molecules and fiber density along electrospun nanofibers without any post spinning treatment. Functionalization with fluorescent molecules demonstrated the efficiency of the method to generate a discontinuous concentration gradient along the aligned fibers. As a proof of concept for tissue engineering, the silk nanofibers were functionalized with increasing concentrations of nerve growth factor (NGF) and the biological activity was assessed and quantified with rat dorsal root ganglion (DRG) neurons cultures. Protein assays showed the absence of passive release of NGF from the functionalized fibers. The results demonstrated that the NGF concentration gradient led to an oriented and increased growth of DRG neurons (417.6 ± 55.7 μm) compared to a single uniform NGF concentration (264.5 ± 37.6 μm). The easy-to-use electrospinning technique combined with the multiple molecules that can be used for fiber functionalization makes this technique versatile for a broad range of applications from biosensors to regenerative medicine.
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Affiliation(s)
- Tony M Dinis
- CNRS UMR 7338: BioMécanique et BioIngénierie Centre de recherche, Université de Technologie de Compiègne , BP 20529 Rue Personne de Roberval, 60205 Compiègne, France
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Li HJ, Zhang X, Zhang F, Wen XH, Lu LJ, Shen J. Enhanced repair effect of toll-like receptor 4 activation on neurotmesis: assessment using MR neurography. AJNR Am J Neuroradiol 2014; 35:1608-1614. [PMID: 24874529 PMCID: PMC7964434 DOI: 10.3174/ajnr.a3977] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Accepted: 01/22/2014] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND PURPOSE Alternative use of molecular approaches is promising for improving nerve regeneration in surgical repair of neurotmesis. The purpose of this study was to determine the role of MR imaging in assessment of the enhanced nerve regeneration with toll-like receptor 4 signaling activation in surgical repair of neurotmesis. MATERIALS AND METHODS Forty-eight healthy rats in which the sciatic nerve was surgically transected followed by immediate surgical coaptation received intraperitoneal injection of toll-like receptor 4 agonist lipopolysaccharide (n = 24, study group) or phosphate buffered saline (n = 24, control group) until postoperative day 7. Sequential T2 measurements and gadofluorine M-enhanced MR imaging and sciatic functional index were obtained over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and gadofluorine enhancement of the distal nerve stumps were measured and compared between nerves treated with lipopolysaccharide and those treated with phosphate buffered saline. RESULTS Nerves treated with lipopolysaccharide injection achieved better functional recovery and showed more prominent gadofluorine enhancement and prolonged T2 values during the degenerative phase compared with nerves treated with phosphate buffered saline. T2 values in nerves treated with lipopolysaccharide showed a more rapid return to baseline level than did gadofluorine enhancement. Histology exhibited more macrophage recruitment, faster myelin debris clearance, and more pronounced nerve regeneration in nerves treated with toll-like receptor 4 activation. CONCLUSIONS The enhanced nerve repair with toll-like receptor 4 activation in surgical repair of neurotmesis can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting such improved nerve regeneration.
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Affiliation(s)
- H J Li
- From the Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - X Zhang
- From the Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - F Zhang
- From the Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - X H Wen
- From the Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - L J Lu
- From the Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - J Shen
- From the Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China.
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28
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Hundepool CA, Nijhuis THJ, Mohseny B, Selles RW, Hovius SER. The effect of stem cells in bridging peripheral nerve defects: a meta-analysis. J Neurosurg 2014; 121:195-209. [PMID: 24816327 DOI: 10.3171/2014.4.jns131260] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
UNLABELLED OBJECT.: For decades the gold standard for reconstructing a large peripheral nerve defect has been, and remains, the nerve autograft. Alternatives to the nerve autograft include biological conduits and vessels. Adding stem cells in the lumen of a nerve conduit has been the subject of multiple studies. The purpose of the present meta-analysis was to summarize animal experimental studies on the effect of stem cells as a luminal additive when reconstructing a peripheral nerve defect with a nerve graft. METHODS A literature search of the MEDLINE and Embase databases was performed from inception to April 2012, searching for animal experiments on peripheral nerve reconstruction models in which a nerve conduit was used with and without the support of 3 different types of stem cells. Stem cells were analyzed according to their origin: bone marrow, adipose tissue, and other origins. Included studies had consistent outcome measurements: walking track analysis, muscle mass ratio, and electrophysiology. RESULTS Forty-four studies were included in the final analysis. Forest plots of the 3 outcome measurements (walking track analysis, muscle mass ratio, and electrophysiology) showed positive effects of stem cells on the regeneration of peripheral nerves at different time points. Almost all comparisons showed significant differences for all 3 stem cells groups compared with a control group in which stem cells were not used. CONCLUSIONS The present report systematically analyzed the different studies that used stem cells as a luminal additive when bridging a large peripheral nerve defect. All 3 different stem cell groups showed a beneficial effect when used in the reconstruction compared with control groups in which stem cells were not used.
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29
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Zhang X, Zhang F, Lu L, Li H, Wen X, Shen J. MR imaging and T2 measurements in peripheral nerve repair with activation of Toll-like receptor 4 of neurotmesis. Eur Radiol 2014; 24:1145-1152. [PMID: 24573569 DOI: 10.1007/s00330-014-3134-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2013] [Revised: 01/21/2014] [Accepted: 02/17/2014] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To investigate the role of MR imaging in neurotmesis combined with surgical repair and Toll-like receptor 4 (TLR4) activation. METHODS Forty-eight rats received subepineurial microinjection of the TLR4 agonist lipopolysaccharide (LPS, n = 24) or phosphate buffered saline (PBS, n = 24) immediately after surgical repair of the transected sciatic nerve. Sequential fat-suppressed T2-weighted imaging and quantitative T2 measurements were obtained at 3, 7, 14 and 21 days after surgery, with histologic assessments performed at regular intervals. T2 relaxation times and histological quantification of the distal stumps were measured and compared. RESULTS The distal stumps of transected nerves treated with LPS or PBS both showed persistent enlargement and hyperintense signal. T2 values of the distal stumps showed a rapid rise to peak level followed by a rapid decline pattern in nerves treated with LPS, while exhibiting a slow rise to peak value followed by a slow decline in nerves treated with PBS. Nerves treated with LPS exhibited more prominent macrophage recruitment, faster myelin debris clearance and more pronounced nerve regeneration. CONCLUSION Nerves treated with TLR4 activation had a characteristic pattern of T2 value change over time. Longitudinal T2 measurements can be used to detect the enhanced repair effect associated with TLR4 activation in the surgical repair of neurotmesis. KEY POINTS • TLR4 activation had additional beneficial effects on neurotmesis beyond surgical repair. • TLR4 activation had a characteristic time course of T2 values. • T2 measurements can help detect beneficial effects with TLR4 activation.
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Affiliation(s)
- Xiang Zhang
- Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou, 510120, Guangdong, China
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Tremp M, Meyer Zu Schwabedissen M, Kappos EA, Engels PE, Fischmann A, Scherberich A, Schaefer DJ, Kalbermatten DF. The regeneration potential after human and autologous stem cell transplantation in a rat sciatic nerve injury model can be monitored by MRI. Cell Transplant 2013; 24:203-11. [PMID: 24380629 DOI: 10.3727/096368913x676934] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Traumatic nerve injuries are a major clinical challenge. Tissue engineering using a combination of nerve conduits and cell-based therapies represents a promising approach to nerve repair. The aim of this study was to examine the regeneration potential of human adipose-derived stem cells (hASCs) after transplantation in a nonautogenous setting and to compare them with autogenous rat ASCs (rASCs) for early peripheral nerve regeneration. Furthermore, the use of MRI to assess the continuous process of nerve regeneration was elaborated. The sciatic nerve injury model in female Sprague-Dawley rats was applied, and a 10-mm gap created by using a fibrin conduit seeded with the following cell types: rASCs, Schwann cell (SC)-like cells from rASC, rat SCs (rSCs), hASCs from the superficial and deep abdominal layer, as well as human stromal vascular fraction (1 × 10(6) cells). As a negative control group, culture medium only was used. After 2 weeks, nerve regeneration was assessed by immunocytochemistry. Furthermore, MRI was performed after 2 and 4 weeks to monitor nerve regeneration. Autogenous ASCs and SC-like cells led to accelerated peripheral nerve regeneration, whereas the human stem cell groups displayed inferior results. Nevertheless, positive trends could be observed for hASCs from the deep abdominal layer. By using a clinical 3T MRI scanner, we were able to visualize the graft as a small black outline and small hyperintensity indicating the regenerating axon front. Furthermore, a strong correlation was found between the length of the regenerating axon front measured by MRI and the length measured by immunocytochemistry (r = 0.74, p = 0.09). We successfully transplanted and compared human and autologous stem cells for peripheral nerve regeneration in a rat sciatic nerve injury model. Furthermore, we were able to implement the clinical 3T MRI scanner to monitor the efficacy of cellular therapy over time.
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Affiliation(s)
- Mathias Tremp
- Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University of Basel Hospital, Basel, Switzerland
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31
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Weise G, Stoll G. Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant? Front Neurol 2012; 3:178. [PMID: 23267343 PMCID: PMC3527731 DOI: 10.3389/fneur.2012.00178] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 12/03/2012] [Indexed: 11/13/2022] Open
Abstract
Unlike other organs the nervous system is secluded from the rest of the organism by the blood brain barrier (BBB) or blood nerve barrier (BNB) preventing passive influx of fluids from the circulation. Similarly, leukocyte entry to the nervous system is tightly controlled. Breakdown of these barriers and cellular inflammation are hallmarks of inflammatory as well as ischemic neurological diseases and thus represent potential therapeutic targets. The spatiotemporal relationship between BBB/BNB disruption and leukocyte infiltration has been a matter of debate. We here review contrast-enhanced magnetic resonance imaging (MRI) as a non-invasive tool to depict barrier dysfunction and its relation to macrophage infiltration in the central and peripheral nervous system under pathological conditions. Novel experimental contrast agents like Gadofluorine M (Gf) allow more sensitive assessment of BBB dysfunction than conventional Gadolinium (Gd)-DTPA enhanced MRI. In addition, Gf facilitates visualization of functional and transient alterations of the BBB remote from lesions. Cellular contrast agents such as superparamagnetic iron oxide particles (SPIO) and perfluorocarbons enable assessment of leukocyte (mainly macrophage) infiltration by MR technology. Combined use of these MR contrast agents disclosed that leukocytes can enter the nervous system independent from a disturbance of the BBB, and vice versa, a dysfunctional BBB/BNB by itself is not sufficient to attract inflammatory cells from the circulation. We will illustrate these basic imaging findings in animal models of multiple sclerosis, cerebral ischemia, and traumatic nerve injury and review corresponding findings in patients.
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Affiliation(s)
- Gesa Weise
- Department of Neurology, University of Wuerzburg Wuerzburg, Germany ; Fraunhofer Institute for Cell Therapy and Immunology Leipzig, Germany ; Translational Center for Regenerative Medicine Leipzig, Germany
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Wang H, Zhao Q, Zhao W, Liu Q, Gu X, Yang Y. Repairing rat sciatic nerve injury by a nerve-growth-factor-loaded, chitosan-based nerve conduit. Biotechnol Appl Biochem 2012; 59:388-94. [PMID: 23586915 DOI: 10.1002/bab.1031] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2012] [Accepted: 07/17/2012] [Indexed: 01/19/2023]
Abstract
We have developed a nerve conduit made up of chitosan, on which nerve growth factor (NGF) was immobilized via genipin cross-linking. The nerve conduit was used to bridge a 10-mm-long sciatic nerve gap in rats. At 24 weeks after surgery, electrophysiological assessment, behavioral analysis, and histological examination were conducted to evaluate the outcomes of peripheral nerve repair. The nerve conduit allowed nerve reconstruction between two stumps and reinnervation of the target gastrocnemius muscle. For two groups of rats repaired respectively by the nerve conduit and autologous nerve graft, the density of regenerated axons was 3.55 ± 0.51 and 3.91 ± 0.14 (P = 0.712), and the cross-sectional area of target muscles was 1,159.68 ± 305.85 and 1,307.06 ± 301.25 (P = 0.922), respectively, without significant differences between the two groups. Our data suggest the feasibility of using chitosan-based, NGF-loaded nerve conduits for peripheral nerve repair.
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Affiliation(s)
- Hongkui Wang
- Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, People's Republic of China
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