Effects of ischemic pre- and postconditioning on cerebral glycogen synthase kinase-3 beta activity in a rat model of cerebral ischemia-reperfusion

Objective To investigate the effects of ischemic pre- and postconditioning on cerebral glycogen synthase kinase-3 beta （GSK-3β） activity in a rat model of global cerebral ischemia-reperfusion （I/R）.Methods Forty male Wistar rats weighing 200-230 g were randomly allocated into 4 groups （n =10 each） ： Ⅰ group sham operation （group S）; Ⅱ group I/R; Ⅲ group ischemic preconditioning （group IPR） and Ⅳ group ischemic postconditioning （group IPO）. The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.4 ml/100 g. Global cerebral ischemia was induced by four-vessel-occlusion in group Ⅱ , Ⅲ and Ⅳ. Bilateral vertebral arteries were cauterized and bilateral carotid arteries were occluded for 10 min. In group IPR cerebral ischemia was preceded by 3 cycles of 10 s ischemia followed by 30 s reperfusion. The group IPO received 3 cycles of 30 s reperfusion followed by 10 s ischemia at the end of 10 min cerebral ischemia. The animals were killed 2 days later. The brains were immediately removed for determination of neuronal apoptosis in the cortex （by TUNEL）, the infarct size （by TTC）, p-GSK-3β activity （by spectrum assay） and the expression of Bcl-2, Bax and Caspase-3 （by SP）. Linear correlation of p-GSK-3β activity with the number of apoptotic neurons in the cortex and cerebral infarct size was analyzed. Results Cerebral I/R significantly increased the number of apoptotic neurons in the cortex and infarct size, decreased p-GSK-3β activity, down-regulated Bcl-2 expression and up-regulated Bax and Caspase-3 expression in group I/R as compared with group S. Ischemic pre- and postconditioning significantly attenuated these cerebral I/R-induced changes. The p-GSK-3β activity was negatively correlated with the number of apoptotic neurons in the cortex and cerebral infarct size. Conclusion Ischemic pre- and postconditioning reduces cerebral I/R injury through inhibiting the activity of GSK-3β. Key words: Ischemic preconditioning; Glycogen synthase kinase 3; Reperfusion injury; Brain; Ischemic postconditioning