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

作者：Jiale He, Yubao Lu, Zengbo Lu, Pan Jiang, Daoqiang Huang, Yiqian Luo, Mao Pang, Bin Liu · 发表于：Medical Gas Research · 年份：2025 · DOI：10.4103/mgr.medgasres-d-25-00034 · 被引用次数：3 · 研究领域：Sulfur Compounds in Biology、Neuroscience of respiration and sleep、Heme Oxygenase-1 and Carbon Monoxide

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 inj...