Hydrogen Sulfide: Neurophysiology and Neuropathology

Hydrogen sulfide (H2S) was known to be a toxic gas and an environmental hazard for many decades. However, it is now recognized that H2S may serve as a gaseous mediator that is endogenously produced to influence biological functions in mammalian. Together with nitric oxide and carbon monoxide, it forms the group of mediators that has been termed the "gasotransmitters." The past decade has seen an exponential growth of scientific interest in the physiological and pathological significance of H2S especially with respect to its role in the central nervous system and the cardiovascular system. In the central nervous system, H2S facilitates long-term potentiation and regulates intracellular calcium concentration and pH level in brain cells. Intriguingly, H2S produces antioxidant, anti-inflammatory, and antiapoptotic effects that may have relevance to neurodegenerative disorders. Abnormal generation and metabolism of H2S have been reported in the pathogenesis of ischemic stroke, Alzheimer's disease, Parkinson's disease, and recurrent febrile seizure. Exogenously applied H2S is demonstrated to have value for the treatment of febrile seizure and Parkinson's disease. This article presents an overview of current knowledge of H2S in relation to brain functions, with a special emphasis on its neuroprotective effects and the underlying cellular and molecular mechanisms. Antioxid. Redox Signal. 15, 405–419.