Hydrogen Sulfide Protects the Brain Against Ischemic Reperfusion Injury in a Transient Model of Focal Cerebral Ischemia

Hydrogen sulfide (H2S), a well-known toxic gas, is regarded as endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. Recent studies have shown relatively high concentrations of hydrogen sulfide (H2S) in the brain and also cytoprotective effects of endogenous and exogenous H2S in models of in vitro and in vivo ischemic injury. H2S protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic mediator and by improving neurological function. Moreover, it protects neurons from glutamate toxicity. Therefore, the present study aimed to determine whether H2S provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and NaHS (H2S donor; 1 and 5 mg) were intraperitoneally injected (IP) at the beginning of ischemia. Infarct volume, brain edema, and apoptosis were assessed 24 h after MCAO. Treatment with NaHS at doses of 1 and 5 mg markedly reduced total infarct volumes by 29 and 51 %, respectively (P < 0.001). In addition, NaHS at doses of 1 and 5 mg reduced brain edema (P < 0.05) and inhibited apoptosis by decreasing positive TUNEL cells (P < 0.001). The present study shows that treatment with H2S reduces brain injuries and postischemic cerebral edema in a dose-dependent manner likely through the blocking programmed cell death. We propose that H2S might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of H2S in stroke patients.