Sevoflurane Preconditioning Confers Neuroprotection via Anti-apoptosis Effects

Neuroprotection against cerebral ischemia afforded by volatile anesthetic preconditioning (APC) has been demonstrated both in vivo and in vitro, yet the underlying mechanism is poorly understood. We previously reported that repeated sevoflurane APC reduced infarct size in rats after focal ischemia. In this study, we investigated whether inhibition of apoptotic signaling cascades contributes to sevoflurane APC-induced neuroprotection. Male Sprague-Dawley rats were exposed to ambient air or 2.4 % sevoflurane for 30 min per day for 4 consecutive days and then subjected to occlusion of the middle cerebral artery (MCAO) for 60 min at 24 h after the last sevoflurane intervention. APC with sevoflurane markedly decreased apoptotic cell death in rat brains, which was accompanied by decreased caspase-3 cleavage and cytochrome c release. The apoptotic suppression was associated with increased ratios of anti-apoptotic Bcl-2 family proteins over pro-apoptotic proteins and with decreased activation of JNK and p53 pathways. Thus, our data suggest that suppression of apoptotic cell death contributes to the neuroprotection against ischemic brain injury conferred by sevoflurane preconditioning.