Postconditioning With Sevoflurane Protects Against Focal Cerebral Ischemia And Reperfusion Injury In Rats

BackgroundFocal brain ischemia is a common perioperation complication in neurosurgery. Emerging evidence has demonstrated that sevoflurane-induced preconditioning protects against cerebral ischemic neuronal damage in rats. However, the onset of focal brain ischemia in patients often is not predictable. Preconditioning is not feasible in clinic. Contrast with preconditioning, postconditioning will have broad applications, which can be applied after the onset of brain ischemia. It has been shown that postconditioning with sevoflurane protects heart against ischemia and reperfusion injury in vivo and in vitro. In this study, we investigated the neuroprotective effect of different concentrations of sevoflurane in rats with middle cerebral artery occlusion (MCAO) 24 hours and 28 days after reperfusion. Furthermore, we tested the hypothesis that the neuroprotective effect of postconditioning with sevoflurane is associated with inhibition of apoptosis and mediated by activation of the PI3K/Akt pathway.MethodsAdult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90 minutes and then treated with sevoflurane at the onset of reperfusion. The infarct volumes, neurological deficit scores and brain edema were evaluated at 24 hours. Spatial learning and memory was examined by Morris water maze on 7 days. The infarct volumes, neurological deficit scores and spatial learning and memory were evaluated on 28 days again. Apoptosis and apoptosis-related proteins were studies by TUNEL, immunohistochemistry and western blot. The neuroprotective effect and the amount of p-Akt after sevoflurane administration with or without wortmannin were analyzed.ResultsPostconditioning with sevoflurane 1.0 MAC and 1.5 MAC significantly decreased neurological deficit scores, infarct volume and brain edema, and markedly improved spatial learning and memory. Sevoflurane 0.5 MAC did not show the neuroprotective effect. Postconditioning with sevoflurane also reduced apoptotic cells, upregulated Bcl-2 and downregulated P53 and Bax. Wortmannin abolished the neuroprotective effect and prevented the increasing of p-Akt. Postconditioning with sevoflurane significantly decreased infarct volume and improved spatial learning and memory on 28 days too, whereas did not help the recovery of neurological deficit scores.ConclusionOur data suggest postconditioning with sevoflurane (1.0 MAC and 1.5 MAC) not only reduced infarct volume but also improved learning and memory. Our study further showed that this neuroprotective effect may be partly due to the activation of PI3K/Akt pathway and inhibiting neuronal apoptosis. Our data support a long-term neuroprotective potency of sevoflurane.