Hydrogen sulfide therapy in brain diseases: from bench to bedside

Hydrogen sulfide (H(2)S) has been recognized and studied for nearly 300 years, but past researches mainly focus on its toxicity effect. During the past two decades, the majority of researches have reported that H(2)S is a novel endogenous gaseous signal molecule in organisms, and play an important role in various systems and diseases. H(2)S is mainly produced by three enzymes, including cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase. H(2)S had been firstly reported as a neuromodulator in the brain, because of its essential role in the facilitating hippocampal long-term potentiation at physiological concentration. It is subsequently reported that H(2)S may have relevance to neurologic disorders through antioxidative, anti-inflammatory, anti-apoptotic and additional effects. Recent basic medical studies and preclinical studies on neurologic diseases have demonstrated that the administration of H(2)S at physiological or pharmacological levels attenuates brain injury. However, the neuroprotective effect of H(2)S is concentration-dependent, only a comparatively low dose of H(2)S can provide beneficial effect. Herein, we review the neuroprotevtive role of H(2)S therapy in brain diseases from its mechanism to clinical application in animal and human subjects, and therefore provide the potential strategies for further clinical treatment.