Abstract
Dexmedetomidine (Dex) has the neuroprotective effect on cerebral ischemia-reperfusion injury (CIRI). But the mechanism is not yet clear. In this study, we established a model of middle cerebral artery occlusion (MCAO) and treated primary cortical neurons with oxygen glucose deprivation (OGD), followed by Dex treatment. Neurological protection of Dex was then assessed by neurological deficit score, brain edema, TTC staining, TUNEL assay, Western blot analysis, immunohistochemistry, and RT-PCR. The results showed that Dex significantly reduced the neurological deficit score, brain edema and cerebral infarction area due to CIRI. After Dex treatment, the expression levels of ER stress-related apoptosis pathway proteins (GRP78, p-PERK, CHOP and Cleaved-caspase-3) were significantly decreased and the apoptosis of brain cells was also significantly reduced. Immunohistochemistry showed that expression and nuclear localization of CHOP decreased significantly after the application of Dex. The downstream apoptotic protein caspase-11 mediated by PERK-CHOP was also markedly inhibited by Dex. In conclusion, our results suggested that Dex reduced ER stress-induced apoptosis after CIRI. Its protective mechanism may be related to PERK-CHOP-Caspase-11 dependent signaling pathway.