Preconditioning with hydrogen sulfide ameliorates cerebral ischemia/reperfusion injury in a mouse model of transient middle cerebral artery occlusion

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. H2S is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous H2S in a mouse model of ischemic stroke. 129P2-Cbs(tm1Unc)/J mice with heterozygous mutants in H2S generating enzyme cystathionine beta-synthase were used to study the effect of endogenous H2S. H2S donor NaHS was used as exogenous H2S. Animals were pretreated with H2S and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-kappa B. Aged 129P2-Cbs(tm1Unc)/J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous H2S treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of H2S was mediated by inhibiting NF-kappa B. Our findings suggest that both endogenous and exogenous H2S are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.