Hydrogen sulfide therapy in brain diseases: from bench to bedside

Hydrogen sulfide (H₂S) 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 H₂S is a novel endogenous gaseous signal molecule in organisms, and play an important role in various systems and diseases. H₂S is mainly produced by three enzymes, including cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase. H₂S 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 H₂S 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 H₂S at physiological or pharmacological levels attenuates brain injury. However, the neuroprotective effect of H₂S is concentration-dependent, only a comparatively low dose of H₂S can provide beneficial effect. Herein, we review the neuroprotevtive role of H₂S 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.