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

Abstract Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. H 2 S 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 H 2 S in a mouse model of ischemic stroke. 129P2-Cbs tm1Unc /J mice with heterozygous mutants in H 2 S generating enzyme cystathionine β-synthase were used to study the effect of endogenous H 2 S. H 2 S donor NaHS was used as exogenous H 2 S. Animals were pretreated with H 2 S 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-κB. Aged 129P2-Cbs tm1Unc /J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous H 2 S treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of H 2 S was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous H 2 S are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.