Mechanisms and therapeutic potential of hydrogen sulfide in traumatic central nervous system injuries.

IF 2.9 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Medical Gas Research Pub Date : 2026-06-01 Epub Date: 2025-08-18 DOI:10.4103/mgr.MEDGASRES-D-25-00034
Jiale He, Yubao Lu, Zengbo Lu, Pan Jiang, Daoqiang Huang, Yiqian Luo, Mao Pang, Bin Liu
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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.

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硫化氢治疗创伤性中枢神经系统损伤的机制及治疗潜力。
创伤性中枢神经系统损伤包括脑和脊髓损伤。最近的研究已经确定硫化氢(H₂S)是一种有效的内源性气体递质,在神经保护和中枢神经系统修复中具有多方面的作用。在这篇系统综述中,我们探讨了H₂S在创伤性中枢神经系统损伤中的作用机制和治疗潜力,并强调了其抗炎、抗氧化和抗凋亡的特性。h2s通过调节核因子- κ B通路抑制炎症,将小胶质细胞极化转变为修复表型。此外,它通过激活核因子红系2相关因子2和雷帕霉素通路的机制靶点,抑制谷氨酸介导的损伤来减轻氧化应激。此外,h2s通过抑制细胞凋亡、铁下垂、焦下垂和自噬来调节细胞死亡,同时促进轴突生长和微血管完整性。新兴的H₂S输送策略,包括GYY4137等缓释供体和先进的水凝胶系统,解决了实现持续和靶向治疗效果的挑战。虽然临床前证据已经证明了基于H₂的治疗方法的前景,但还需要进一步的研究来优化给药方法,调查浓度依赖性效应,并验证临床疗效。本文综述为进一步推进H₂S作为外伤性中枢神经系统损伤的治疗剂提供了全面的基础。
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来源期刊
Medical Gas Research
Medical Gas Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
5.10
自引率
13.80%
发文量
35
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.
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