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Lin F, Li R, Chen Y, Yang J, Wang K, Jia Y, Han H, Hao Q, Shi G, Wang S, Zhao Y, Chen X. Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial. Trials 2024; 25:377. [PMID: 38863026 PMCID: PMC11167899 DOI: 10.1186/s13063-024-08231-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 05/21/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.
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Affiliation(s)
- Fa Lin
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Runting Li
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yu Chen
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Jun Yang
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ke Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yitong Jia
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Heze Han
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Qiang Hao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Guangzhi Shi
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shuo Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Stroke Center, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Yuanli Zhao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Stroke Center, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xiaolin Chen
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, China.
- China National Clinical Research Center for Neurological Diseases, Beijing, China.
- Stroke Center, Beijing Institute for Brain Disorders, Beijing, China.
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China.
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Peng Z, Li XJ, Zhou Y, Zhang JT, Zhu Q, Sun JQ, Hang CH, Li W, Zhang QR, Zhuang Z. Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation. Free Radic Biol Med 2024; 215:79-93. [PMID: 38447853 DOI: 10.1016/j.freeradbiomed.2024.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/01/2024] [Accepted: 02/29/2024] [Indexed: 03/08/2024]
Abstract
OBJECTIVE Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.
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Affiliation(s)
- Zheng Peng
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Xiao-Jian Li
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Yan Zhou
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Jia-Tong Zhang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Qi Zhu
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Jia-Qing Sun
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Chun-Hua Hang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Wei Li
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China.
| | - Qing-Rong Zhang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China.
| | - Zong Zhuang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China.
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Liang X, Kurboniyon MS, Zou Y, Luo K, Fang S, Xia P, Ning S, Zhang L, Wang C. GSH-Triggered/Photothermal-Enhanced H 2S Signaling Molecule Release for Gas Therapy. Pharmaceutics 2023; 15:2443. [PMID: 37896203 PMCID: PMC10610203 DOI: 10.3390/pharmaceutics15102443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/29/2023] [Accepted: 10/03/2023] [Indexed: 10/29/2023] Open
Abstract
Traditional treatment methods for tumors are inefficient and have severe side effects. At present, new therapeutic methods such as phototherapy, chemodynamic therapy, and gasodynamic therapy have been innovatively developed. High concentrations of hydrogen sulfide (H2S) gas exhibit cancer-suppressive effects. Herein, a Prussian blue-loaded tetra-sulfide modified dendritic mesoporous organosilica (PB@DMOS) was rationally constructed with glutathione (GSH)-triggered/photothermal-enhanced H2S signaling molecule release properties for gas therapy. The as-synthesized nanoplatform confined PB nanoparticles in the mesoporous structure of organosilica silica due to electrostatic adsorption. In the case of a GSH overexpressed tumor microenvironment, H2S gas was controllably released. And the temperature increases due to the photothermal effects of PB nanoparticles, further enhancing H2S release. At the same time, PB nanoparticles with excellent hydrogen peroxide catalytic performance also amplified the efficiency of tumor therapy. Thus, a collective nanoplatform with gas therapy/photothermal therapy/catalytic therapy functionalities shows potential promise in terms of efficient tumor therapy.
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Affiliation(s)
- Xinqiang Liang
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | | | - Yuanhan Zou
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | - Kezong Luo
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | - Shuhong Fang
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | - Pengle Xia
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | - Shufang Ning
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | - Litu Zhang
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
| | - Chen Wang
- Department of Research, Guangxi Cancer Molecular Medicine Engineering Research Center, Guangxi Medical University Cancer Hospital, Nanning 530021, China; (X.L.); (Y.Z.); (K.L.); (S.F.); (P.X.); (S.N.)
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Ramanathan D, Huang L, Wilson T, Boling W. Molecular hydrogen therapy for neurological diseases: a review of current evidence. Med Gas Res 2022; 13:94-98. [PMID: 36571372 PMCID: PMC9979207 DOI: 10.4103/2045-9912.359677] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Reactive oxygen species and other free radicals cause oxidative stress which is the underlying pathogenesis of cellular injury in various neurological diseases. Molecular hydrogen therapy with its unique biological property of selectively scavenging pathological free radicals has demonstrated therapeutic potential in innumerable animal studies and some clinical trials. These studies have implicated several cellular pathways affected by hydrogen therapy in explaining its anti-inflammatory and antioxidative effects. This article reviews relevant animal and clinical studies that demonstrate neuroprotective effects of hydrogen therapy in stroke, neurodegenerative diseases, neurotrauma, and global brain injury.
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Affiliation(s)
- Dinesh Ramanathan
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA
| | - Lei Huang
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA,Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USA
| | - Taylor Wilson
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA
| | - Warren Boling
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA,Correspondence to: Warren Boling, E-mail:
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Mu Q, Lv K, Yu J, Chu S, Zhang L, Kong L, Zhang L, Tian Y, Jia X, Liu B, Wei Y, Yang N. Hydrogen Repairs LPS-Induced Endothelial Progenitor Cells Injury via PI3K/AKT/eNOS Pathway. Front Pharmacol 2022; 13:894812. [PMID: 35645804 PMCID: PMC9133378 DOI: 10.3389/fphar.2022.894812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 04/21/2022] [Indexed: 11/15/2022] Open
Abstract
Endotoxins and other harmful substances may cause an increase in permeability in endothelial cells (ECs) monolayers, as well as ECs shrinkage and death to induce lung damage. Lipopolysaccharide (LPS) can impair endothelial progenitor cells (EPCs) functions, including proliferation, migration, and tube formation. EPCs can migrate to the damaged area, differentiate into ECs, and participate in vascular repair, which improves pulmonary capillary endothelial dysfunction and maintains the integrity of the endothelial barrier. Hydrogen (H2) contributes to the repairment of lung injury and the damage of ECs. We therefore speculate that H2 protects the EPCs against LPS-induced damage, and it's mechanism will be explored. The bone marrow-derived EPCs from ICR Mice were treated with LPS to establish a damaged model. Then EPCs were incubated with H2, and treated with PI3K inhibitor LY294002 and endothelial nitric oxide synthase (eNOS) inhibitor L-NAME. MTT assay, transwell assay and tube formation assay were used to detect the proliferation, migration and angiogenesis of EPCs. The expression levels of target proteins were detected by Western blot. Results found that H2 repaired EPCs proliferation, migration and tube formation functions damaged by LPS. LY294002 and L-NAME significantly inhibited the repaired effect of H2 on LPS-induced dysfunctions of EPCs. H2 also restored levels of phosphor-AKT (p-AKT), eNOS and phosphor-eNOS (p-eNOS) suppressed by LPS. LY294002 significantly inhibited the increase of p-AKT and eNOS and p-eNOS expression exposed by H2. L-NAME significantly inhibited the increase of eNOS and p-eNOS expression induced by H2. H2 repairs the dysfunctions of EPCs induced by LPS, which is mediated by PI3K/AKT/eNOS signaling pathway.
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Affiliation(s)
- Qingjie Mu
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- University of Health and Rehabilitation Sciences, Qingdao, China
| | - Kaixuan Lv
- School of Bioscience and Technology, Weifang Medical University, Weifang, China
| | - Jielun Yu
- School of Bioscience and Technology, Weifang Medical University, Weifang, China
- Medical Laboratory Animal Center, Weifang Medical University, Weifang, China
- Weifang Key Laboratory of Animal Model Research on Cardiovascular and Cerebrovascular Diseases, Weifang, China
| | - Shangmin Chu
- School of Bioscience and Technology, Weifang Medical University, Weifang, China
| | - Lichun Zhang
- School of Bioscience and Technology, Weifang Medical University, Weifang, China
| | - Lingyu Kong
- School of Rehabilitation Medicine, Weifang Medical University, Weifang, China
| | - Linlin Zhang
- School of Bioscience and Technology, Weifang Medical University, Weifang, China
| | - Yan Tian
- Research Center of Translational Medicine Shanghai East Hospital, Tongji University, Shanghai, China
| | - Xiaopeng Jia
- Shandong Qilu Stem Cell Engineering Co., Jinan, China
| | - Benhong Liu
- Department of Respiratory, Dongying People's Hospital, Dongying, China
| | - Youzhen Wei
- Research Center for Translational Medicine and Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Nana Yang
- School of Bioscience and Technology, Weifang Medical University, Weifang, China
- Medical Laboratory Animal Center, Weifang Medical University, Weifang, China
- Weifang Key Laboratory of Animal Model Research on Cardiovascular and Cerebrovascular Diseases, Weifang, China
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Huang Y, Xiao FM, Tang WJ, Qiao J, Wei HF, Xie YY, Wei YZ. Hydrogen inhalation promotes recovery of a patient in persistent vegetative state from intracerebral hemorrhage: A case report and literature review. World J Clin Cases 2022; 10:1311-1319. [PMID: 35211564 PMCID: PMC8855194 DOI: 10.12998/wjcc.v10.i4.1311] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/05/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Persistent vegetative state (PVS) is a devastating and long-lasting clinical condition with high morbidity and mortality; currently, there are no available effective interventions.
CASE SUMMARY We report the case of an 11-year-old boy with PVS caused by severe intracerebral bleeding in the left hemisphere following anticoagulation treatment. The patient’s PVS severity showed no notable improvement after 2-mo neuroprotective treatment and rehabilitation, including nerve growth factor and baclofen, hyperbaric oxygen, and comprehensive bedside rehabilitation therapies. Daily inhalation treatment (4-6 h) of high-concentration hydrogen (H2) gas (66.6% H2 + 33.3% O2) was provided. Surprisingly, the patient’s orientation, consciousness, ability to speak, facial expressions, and locomotor function were significantly restored, along with improvements in essential general health status, after H2 gas inhalation treatment, which was consistent with stabilized neuropathology in the left hemisphere and increased Hounsfield unit values of computed tomography in the right hemisphere. The patient finally recovered to a near normal conscious state with a Coma Recovery Scale-Revised Score of 22 from his previous score of 3.
CONCLUSION Phase 1 clinical trials are needed to explore the safety and efficacy of H2 gas inhalation in patients with PVS.
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Affiliation(s)
- Yan Huang
- Department of Rehabilitation, Qilu Children’s Hospital of Shandong University, Jinan 250022, Shandong Province, China
| | - Feng-Ming Xiao
- Department of Rehabilitation, Qilu Children’s Hospital of Shandong University, Jinan 250022, Shandong Province, China
| | - Wen-Jie Tang
- Research Center for Translational Medicine & Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, Shanghai Province, China
| | - Jing Qiao
- Department of Pediatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, Shanghai Province, China
| | - Hai-Feng Wei
- Department of Clinical Imaging, The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250022, Shandong Province, China
| | - Yuan-Yun Xie
- National Clinic and Medicine Research Institute for Geriatric Diseases, Gannan Health Promotion and Translational Laboratory, The First Affiliated Hospital, Gannan University of Medical Sciences, Ganzhou 341000, Jiangxi Province, China
| | - You-Zhen Wei
- Research Center for Translational Medicine & Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, Shanghai Province, China
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Lin F, Li R, Tu WJ, Chen Y, Wang K, Chen X, Zhao J. An Update on Antioxidative Stress Therapy Research for Early Brain Injury After Subarachnoid Hemorrhage. Front Aging Neurosci 2021; 13:772036. [PMID: 34938172 PMCID: PMC8686680 DOI: 10.3389/fnagi.2021.772036] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/08/2021] [Indexed: 12/30/2022] Open
Abstract
The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.
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Affiliation(s)
- Fa Lin
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Runting Li
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Wen-Jun Tu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- The General Office of Stroke Prevention Project Committee, National Health Commission of the People’s Republic of China, Beijing, China
- Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China
| | - Yu Chen
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Ke Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Xiaolin Chen
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
| | - Jizong Zhao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
- Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China
- Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
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Jiang B, Li Y, Dai W, Wu A, Wu H, Mao D. Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage. Acta Cir Bras 2021; 36:e360804. [PMID: 34644772 PMCID: PMC8516430 DOI: 10.1590/acb360804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 07/20/2021] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Subarachnoid hemorrhage (SAH) is a common complication of cerebral vascular disease. Hydrogen has been reported to alleviate early brain injury (EBI) through oxidative stress injury, reactive oxygen species (ROS), and autophagy. Autophagy is a programmed cell death mechanism that plays a vital role in neuronal cell death after SAH. However, the precise role of autophagy in hydrogen-mediated neuroprotection following SAH has not been confirmed. METHODS In the present study, the objective was to investigate the neuroprotective effects and potential molecular mechanisms of hydrogen-rich saline in SAH-induced EBI by regulating neural autophagy in the C57BL/6 mice model. Mortality, neurological score, brain water content, ROS, malondialdehyde (MDA), and neuronal death were evaluated. RESULTS The results show that hydrogen-rich saline treatment markedly increased the survival rate and neurological score, increased neuron survival, downregulated the autophagy protein expression of Beclin-1 and LC3, and endoplasmic reticulum (ER) stress. That indicates that hydrogen-rich saline-mediated inhibition of autophagy and ER stress ameliorate neuronal death after SAH. The neuroprotective capacity of hydrogen-rich saline is partly dependent on the ROS/Nrf2/heme oxygenase-1 (HO-1) signaling pathway. CONCLUSIONS The results of this study demonstrate that hydrogen-rich saline improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and ER stress.
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Affiliation(s)
| | | | | | - An Wu
- Wenzhou Medical University, China
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Huang L, Lenahan C, Boling W, Tang J, Zhang JH. Molecular Hydrogen Application in Stroke: Bench to Bedside. Curr Pharm Des 2021; 27:703-712. [PMID: 32940172 DOI: 10.2174/1381612826666200917152316] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 07/27/2020] [Indexed: 11/22/2022]
Abstract
Stroke is a major cause of mortality and morbidity worldwide. Effective treatments are limited. Molecular hydrogen is emerging as a novel medical gas with therapeutic potential for various neurological diseases, including stroke. We reviewed the experimental and clinical findings of the effects of molecular hydrogen therapy in stroke patients and models. The underlying neuroprotective mechanisms against stroke pathology were also discussed.
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Affiliation(s)
- Lei Huang
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA92354, United States
| | - Cameron Lenahan
- Center for Neuroscience Research, Loma Linda University School of Medicine, Loma Linda, CA, 92324, United States
| | - Warren Boling
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA92354, United States
| | - Jiping Tang
- Center for Neuroscience Research, Loma Linda University School of Medicine, Loma Linda, CA, 92324, United States
| | - John H Zhang
- Department of Neurosurgery, Loma Linda University, Loma Linda, CA92354, United States
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Abstract
Traumatic brain injury (TBI) is a serious global public health problem. Survivors of TBI often suffer from long-term disability, which puts a heavy burden on society and families. Unfortunately, up to now, there is no efficacious treatment for TBI patients in clinical practice. As a reducing gas, hydrogen has been shown to be neuroprotective in multiple cerebral disease models; however, its efficacy in TBI remains controversial. In this review, we will focus on the results of hydrogen in experimental TBI, elaborate the potential mechanisms, and put forward for future researches based on our current understanding and views.
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Affiliation(s)
- Hong-Wei Hu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Zhi-Guo Chen
- Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Jian-Gang Liu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Gang Chen
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
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Hydrogen: A Novel Option in Human Disease Treatment. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8384742. [PMID: 32963703 PMCID: PMC7495244 DOI: 10.1155/2020/8384742] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 06/06/2020] [Accepted: 07/13/2020] [Indexed: 02/08/2023]
Abstract
H2 has shown anti-inflammatory and antioxidant ability in many clinical trials, and its application is recommended in the latest Chinese novel coronavirus pneumonia (NCP) treatment guidelines. Clinical experiments have revealed the surprising finding that H2 gas may protect the lungs and extrapulmonary organs from pathological stimuli in NCP patients. The potential mechanisms underlying the action of H2 gas are not clear. H2 gas may regulate the anti-inflammatory and antioxidant activity, mitochondrial energy metabolism, endoplasmic reticulum stress, the immune system, and cell death (apoptosis, autophagy, pyroptosis, ferroptosis, and circadian clock, among others) and has therapeutic potential for many systemic diseases. This paper reviews the basic research and the latest clinical applications of H2 gas in multiorgan system diseases to establish strategies for the clinical treatment for various diseases.
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