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

Abstract

Hydrogen sulfide (H(2)S), 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 (H(2)S) in the brain and also cytoprotective effects of endogenous and exogenous H(2)S in models of in vitro and in vivo ischemic injury. H(2)S 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 H(2)S 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 (H(2)S 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 H(2)S reduces brain injuries and postischemic cerebral edema in a dose-dependent manner likely through the blocking programmed cell death.We propose that H(2)S might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of H(2)S in stroke patients.

Hydrogen sulfide induces neuroprotection against experimental stroke in rats by down-regulation of AQP4 via activating PKC

“…Gheibi et al (2014) reported that 1 and 5 mg NaHS (an H 2 S donor) intraperitoneally injected at the beginning of ischemia reduced brain edema in a dose-dependent manner. However, Johansen et al (2006) demonstrated that the concentrationdependent protective action of NaHS was not observed at 10 μM in the perfused heart model.…”

Hydrogen Sulfide Decreases Blood-Brain Barrier Damage via Regulating Protein Kinase C and Tight Junction After Cardiac Arrest in Rats

“…confirmed that the protective effect of NaHS on myocardium against ischemic/ reperfusion injury protection was not concentration-dependent. While the study of Gheibi et al [50]. in which a MCAO model was applied, the authors found that intraperitoneal injection of NaHS alleviated brain edema and the protective effect was dose-dependent.…”

Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation

“…DNA fragmentation and apoptotic cell death were detected using a TUNEL assay [26,27]. TUNEL staining was performed using an In Situ Cell Death Detection Kit (Roche, Mannheim, Germany), a kit for the detection and quantification of apoptosis on the single cell level, based on labeling of DNA stand breaks, according to the manufacturer's protocol.…”