Preconditioning of H2S inhalation protects against cerebral ischemia/reperfusion injury by induction of HSP70 through PI3K/Akt/Nrf2 pathway

•H2S preconditioning exhibited significant neuroprotection against cerebral I/R.•The protective effect of H2S preconditioning involves heat shock protein 70 (HSP70).•HSP70 protects mice against cerebral I/R through PI3K/Akt/Nrf2 pathway. It is of great importance to protect the brain against cerebral ischemia and reperfusion (I/R) injury, which leads to excitotoxicity, redox imbalance, inflammation and apoptosis; however, there is currently no effective treatment. The present study aimed to investigate the effect of H2S preconditioning on cerebral I/R injury and its underlying mechanism. The results demonstrated that H2S preconditioning significantly prevented the development of neurological function abnormality, inflammation and oxidative injury in mice as well as cognitive impairment caused by cerebral I/R. H2S preconditioning also suppressed the apoptosis caused by cerebral I/R. Moreover, the protective effect of H2S preconditioning was found to involve heat shock protein 70 (HSP70), in which the PI3K/Akt/Nrf2 pathway was involved. The data showed that H2S preconditioning could protect mice against cerebral I/R injury by the induction of HSP70 and the PI3K/Akt/Nrf2 pathway.