Dynamic change of hydrogen sulfide during global cerebral ischemia–reperfusion and its effect in rats

Abstract

Hydrogen sulfide (H 2S) is a gaseous messenger and serves as an important neuromodulator in central nervous system. In the current study, we investigated the change of H 2S and cystathionine β-synthase (CBS), an H 2S-synthesizing enzyme at different time points of reperfusion following global cerebral ischemia in rats, and the effect of exogenous H 2S on global cerebral ischemia–reperfusion injury. First, we used global cerebral ischemia–reperfusion model by occlusion of bilateral common carotid arteries and vertebral arteries. Next, we measured H 2S levels in the hippocampus, cortex and plasma, the activity of H 2S-synthesizing enzymes and expression of CBS mRNA and protein in the hippocampus and cortex at 12 h, 24 h, 48 h, 72 h and 7 days of reperfusion following 15 min cerebral ischemia. Second, we pretreated rats with different doses of sodium hydrogen sulfide (NaHS), an H 2S donor and observed its effect on neuronal injury induced by 7 days of reperfusion after 15 min global cerebral ischemia. We found that when compared to sham group the amount of H 2S in the hippocampus was increased significantly at 12 h of reperfusion after cerebral ischemia, markedly decreased at 24 h, restored to the same level as that in sham group at 48 h and maintained at 72 h and 7 days. The same change tendency in the levels of H 2S was found in the cortex as described for the hippocampus. We found a similar change tendency in the activity of H 2S-synthesizing enzymes, CBS mRNA and protein expression to that in the H 2S level at different time points of reperfusion. Furthermore, while 180 μmol/kg NaHS pretreatment deteriorated the neuronal injury after global cerebral ischemia, 25 μmol/kg NaHS attenuated the neuronal injury. We suggest that a decrease of H 2S level at 24 h of reperfusion after global cerebral ischemia may be involved in neuronal injury after cerebral ischemia and lower concentration rather than higher concentration of exogenous H 2S may offer a protection against the neuronal injury induced by global cerebral ischemia–reperfusion.