| Objective To investigate whether remote ischemic postconditioning (RIPoC) could protect brain against global cerebral ischemia/reperfusion (I/R) injury. Methods:Adult male Sprague-Dawley rats weighing200-250g were randomly divided into four groups:sham group, I/R group, I/R+RIPoC group and RIPoC group. Global cerebra I/R induced neuronal injury was quantified by counting the neuronal density (ND) in the hippocampal CA1region and the parietal cortex at7d of reperfusion, and behaviorally by evaluating the spatial learning and memory deficit in Morris water maze task from4d to7d of reperfusion. Results:Extensive neuronal death after4-VO was significantly attenuated by RIPoC. RIPoC reduced neuronal loss and attenuated spatial learning and memory deficit (P<0.05). Conclusion:RIPoC could protect brain against global cerebral I/R injury by reducing delayed neuronal death and attenuating the spatial learning and memory deficit. Part II Effects of remote ischemic postconditioning on the related molecules in brain[Abstract] Objective To investigate whether the protection of remote ischemic postconditioning (RIPoC) is related to oxidative stress and apoptosis-related proteins.Methods:Adult male Sprague-Dawley rats weighing200-250g were randomly divided into four groups:sham group, I/R group, I/R+RIPoC group and RIPoC group. All groups were further divided into2subgroups:24h and48h. Global cerebra I/R induced apoptosis was examined using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, and apoptosis-related proteins Bcl-2and Bax were studied by immunohistochemistry and Western blot at24h and48h of reperfusion. Furthermore, we examined the activities of superoxide dismutase (SOD), catalase (CAT), and the level of malondialdehyde (MDA) at48of reperfusion. Results:Extensive neuronal death after4-VO was significantly attenuated by RIPoC. RIPoC reduced the number of TUNEL positive cells (P<0.01), RIPoC upregulated Bcl-2expression, downregulated Bax expression in CA1region (P<0.01), and reduced oxidative stress levels in CA1region and cortex (P<0.01). Conclusion: RIPoC could protect brain against global cerebral I/R injury by reducing apoptosis and ameliorating oxidative stress. PartⅢ Remote ischemic postconditioning protects against global cerebral ischemia/reperfusion injury by up-regulating eNOS Via PI3K/Akt pathway in rats[Abstract] Objective To investigate the roles of eNOS and PI3K/Akt pathway in the neuroprotection of remote ischemic postconditioning (RIPoC) on global cerebral ischemia reperfusion (I/R) injury in rats. Methods One hundred male adult SD rats weighing200-250g were randomly divided into5groups (n=20each):group sham, group I/R, group I/R+RIPoC, group L-NAME+I/R+RIPoC, group LY+I/R+RIPoC. Global cerebral I/R was induced by four-vessel occlusion. Group I/R+RIPoC, group L-NAME+I/R+RIPoC and group LY+I/R+RIPoC received3cycles of15min reperfusion followed by15min ischemia in bilateral femoral arteries at the beginning of cerebral reperfusion. The rats were sacrificed at48h of cerebral reperfusion, and brains were removed for determination of neuronal apoptosis (by TUNEL method) in hippocampal CA1region and p-eNOS, eNOS, p-Akt and Akt expression (by Western blot) in hippocampal CA1region. Morris water maze task was used to test the learning and memory function at4d of cerebral reperfusion, and the rats were sacrificed at7d of cerebral reperfusion, and brains were removed for determination of neuronal density in hippocampal CA1region. Results Cerebral I/R significantly increased the number of apoptotic neurons and learning and memory function in group I/R as compared with group sham. RIPoC significantly attenuated these cerebral I/R-induced changes. Pre-administration of N(ω)-nitro-l-arginine methyl ester (a nonselective NOS inhibitor) significantly abolished the neuroprotective effect of RIPoC. Moreover, pre-administration of LY294002(a highly selective inhibitor of PI3K) not only significantly reversed the neuroprotective effect of RIPoC, but also obviously inhibited the up-regulation of eNOS induced by RIPoC.Conclusion RIPoC protects the brain against global cerebral I/R injury and that this neuroprotection is mediated by up-regulating eNOS through the PI3K/Akt pathway. |
