Jiale He, Yubao Lu, Zengbo Lu, Pan Jiang, Daoqiang Huang, Yiqian Luo, Mao Pang, Bin Liu
{"title":"Mechanisms and therapeutic potential of hydrogen sulfide in traumatic central nervous system injuries.","authors":"Jiale He, Yubao Lu, Zengbo Lu, Pan Jiang, Daoqiang Huang, Yiqian Luo, Mao Pang, Bin Liu","doi":"10.4103/mgr.MEDGASRES-D-25-00034","DOIUrl":null,"url":null,"abstract":"<p><p>Traumatic central nervous system injuries encompass brain and spinal cord injuries. Recent studies have identified hydrogen sulfide (H₂S) as a potent endogenous gasotransmitter with multifaceted roles in neuroprotection and central nervous system repair. In this systematic review, we explore the mechanisms and therapeutic potential of H₂S in traumatic central nervous system injuries, emphasizing its anti-inflammatory, antioxidant, and anti-apoptotic properties. H₂S suppresses inflammation by modulating the nuclear factor-kappa B pathway, shifting microglial polarization to a reparative phenotype. Further, it mitigates oxidative stress by activating the nuclear factor erythroid 2-related factor 2 and mechanistic target of the rapamycin pathway, and inhibiting glutamate-mediated damage. Additionally, H₂S regulates cell death by inhibiting apoptosis, ferroptosis, pyroptosis, and autophagy while promoting axonal growth and microvascular integrity. Emerging H₂S delivery strategies, including slow-releasing donors such as GYY4137 and advanced hydrogel-based systems, address challenges in achieving sustained and targeted therapeutic effects. Although preclinical evidence has demonstrated the promise of H₂S-based therapies, further research is required to optimize delivery methods, investigate concentration-dependent effects, and validate clinical efficacy. This review provides a comprehensive foundation for advancing H₂S as a therapeutic agent in traumatic central nervous system injuries.</p>","PeriodicalId":18559,"journal":{"name":"Medical Gas Research","volume":"16 2","pages":"148-155"},"PeriodicalIF":2.9000,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413885/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Gas Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/mgr.MEDGASRES-D-25-00034","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/18 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Traumatic central nervous system injuries encompass brain and spinal cord injuries. Recent studies have identified hydrogen sulfide (H₂S) as a potent endogenous gasotransmitter with multifaceted roles in neuroprotection and central nervous system repair. In this systematic review, we explore the mechanisms and therapeutic potential of H₂S in traumatic central nervous system injuries, emphasizing its anti-inflammatory, antioxidant, and anti-apoptotic properties. H₂S suppresses inflammation by modulating the nuclear factor-kappa B pathway, shifting microglial polarization to a reparative phenotype. Further, it mitigates oxidative stress by activating the nuclear factor erythroid 2-related factor 2 and mechanistic target of the rapamycin pathway, and inhibiting glutamate-mediated damage. Additionally, H₂S regulates cell death by inhibiting apoptosis, ferroptosis, pyroptosis, and autophagy while promoting axonal growth and microvascular integrity. Emerging H₂S delivery strategies, including slow-releasing donors such as GYY4137 and advanced hydrogel-based systems, address challenges in achieving sustained and targeted therapeutic effects. Although preclinical evidence has demonstrated the promise of H₂S-based therapies, further research is required to optimize delivery methods, investigate concentration-dependent effects, and validate clinical efficacy. This review provides a comprehensive foundation for advancing H₂S as a therapeutic agent in traumatic central nervous system injuries.
期刊介绍:
Medical Gas Research is an open access journal which publishes basic, translational, and clinical research focusing on the neurobiology as well as multidisciplinary aspects of medical gas research and their applications to related disorders. The journal covers all areas of medical gas research, but also has several special sections. Authors can submit directly to these sections, whose peer-review process is overseen by our distinguished Section Editors: Inert gases - Edited by Xuejun Sun and Mark Coburn, Gasotransmitters - Edited by Atsunori Nakao and John Calvert, Oxygen and diving medicine - Edited by Daniel Rossignol and Ke Jian Liu, Anesthetic gases - Edited by Richard Applegate and Zhongcong Xie, Medical gas in other fields of biology - Edited by John Zhang. Medical gas is a large family including oxygen, hydrogen, carbon monoxide, carbon dioxide, nitrogen, xenon, hydrogen sulfide, nitrous oxide, carbon disulfide, argon, helium and other noble gases. These medical gases are used in multiple fields of clinical practice and basic science research including anesthesiology, hyperbaric oxygen medicine, diving medicine, internal medicine, emergency medicine, surgery, and many basic sciences disciplines such as physiology, pharmacology, biochemistry, microbiology and neurosciences. Due to the unique nature of medical gas practice, Medical Gas Research will serve as an information platform for educational and technological advances in the field of medical gas.