Hydrogen Sulfide: Neurophysiology and Neuropathology

Hydrogen sulfide (H(2)S) was known to be a toxic gas and an environmental hazard for many decades. However, it is now recognized that H(2)S 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 H(2)S especially with respect to its role in the central nervous system and the cardiovascular system. In the central nervous system, H(2)S facilitates long-term potentiation and regulates intracellular calcium concentration and pH level in brain cells. Intriguingly, H(2)S produces antioxidant, anti-inflammatory, and antiapoptotic effects that may have relevance to neurodegenerative disorders. Abnormal generation and metabolism of H(2)S have been reported in the pathogenesis of ischemic stroke, Alzheimer's disease, Parkinson's disease, and recurrent febrile seizure. Exogenously applied H(2)S is demonstrated to have value for the treatment of febrile seizure and Parkinson's disease. This article presents an overview of current knowledge of H(2)S 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.