Postconditioning With Sevoflurane Exerts Neuroprotection By Inhibiting PTEN To Enhance Activation Of PI3K/AKT Signaling In Rats

In this study, we investigated the neuroprotective effect and the potentialmechanism of sevoflurane postconditioning in rats with middle cerebral arteryocclusion (MCAO).Adult male Sprague-Dawley rats were subjected to MCAO for90min and then treated with sevoflurane at the beginning of reperfusion. Theneurological deficit scores(NDS) and the infarct volume were evaluated by2,3,5-triphenyltetrazolium chloride(TTC)staining at24hours of reperfusion.Apoptosis and apoptosis-related proteins were studied by TUNEL staining andwestern blot.1. Postconditioning with sevoflurane protects against focal cerebralischemia/reperfusion injuryAdult male Sprague-Dawley rats were subjected to the right middle cerebralartery occlusion (MCAO). The animals in0.5,1.0and1.5MAC group were given0.5,1.0and1.5MAC sevoflurane inhalation for30minutes at the onset of reperfusion.The neurological deficit scores（NDS）and the percentage of infarct volumes andTUNEL-positive cells were evaluated at24hours after reperfusion.Postconditioningwith1.0MAC and1.5MAC sevoflurane significantly decreased neurological deficitscores, infarct volume and theTUNEL-positive cells, but0.5MAC sevoflurane didnot show the neuroprotective effect.2. Temporal courses of the expression and phosphorylation of PTEN and Akt inthe ischemia penumbra regions following focal cerebral ischemia/reperfusionFocal cerebral ischemia/reperfusion injury was induced by the the right middlecerebral artery occlusion (MCAO).Time courses of the expression and thephosphorylation of PTEN and Akt in the ischemia penumbra regions were evaluatedat0min、30min、3h、6h、12h、24h and72h of reperfusion by western blot.The proteinexpression of p-Akt was remarkably increased over the control levels from30min to12h of reperfusion, and returned to the control level at24h, with no secondaryincrease at72h of reperfusion. The protein expression of p-PTEN was remarkablyincreased over the control levels from30min to12h of reperfusion, and returned tothe control level at24h, with no secondary increase at72h of reperfusion.Theseobservations suggest that there might be some relationship between PTEN and Akt pathways during ischemic reperfusion.3. Postconditioning with sevoflurane exerts neuroprotection by inhibiting PTENto enhance Akt expression in ratsAdult male Sprague-Dawley rats were subjected to the right middle cerebralartery occlusion (MCAO). Rats in sevoflurane postconditioning group were given1.0MAC sevoflurane inhalation for30minutes at the onset of reperfusion. Pic (theselective inhibitor of PTEN) was dissolved in normal saline for intraperitonealinjection at dose of20μg/100g every three hours for four times before MCAO. TheNDS, the percentage of infarct volumes, which were assayed by TTC staining,and theTUNEL-positive cells were adopted to assess the cerebral injury at24hours afterreperfusion. The amount of phosphorylated PTEN and phosphorylated Akt wereanalyzed by western blot at24hours after reperfusion. Intraperitoneal injection picand postconditioning with sevoflurane both decreased NDS,infract volume andTUNEL-positive cells, and the expression of phosphorylated Akt and PTEN wereup-regulated.But intraperitoneal injection with pic andpostconditioning withsevoflurane at the same time did not show the better neuroprotection effect. Theenhancement of PI3K/Akt signal pathway by inhibiting PTEN is involved in theprotective effect of sevoflurane postconditioning against focal cerebralischemia/reperfusion injury．...