Effects of Focal Ischemia Preconditioning on VEGF Expression and Angiogenesis in Rats with Cerebral Ischemia

Aim: To investigate the effects of focal ischemia preconditioning on vascular endothelial growth factor(VEGF) expression and angiogenesis in rats with cerebral ischemia.Methods: Healthy Wistar rats were randomly assigned to three groups: sham surgery,non-ischemic preconditioning(NIP),and ischemic preconditioning(IP).For ischemic preconditioning,the rats were given middle cerebral artery occlusion(MCAO) for 10 min.In the IP group,rat models of pre-ischemia-reperfusion-ischemia-reperfusion were established by MCAO using the twice suture method.In the NIP group,pre-ischemia was replaced by sham surgery.Subsequently,the latter two groups were equally divided into five subgroups according to the time of first reperfusion,including 1,3,7,14,21 day subgroups.The sham surgery group received the sham surgerytwice.Brain sections were stained with TTC for surveying the volume of infraction.The expression of microvascular density(MVD)and VEGF were determined by immunohistochemical staining and in situ hybridization respectively.Results: ① Intergroup comparison: compared with the NIP group,neurologic deficit scores and infarct volume significantly decreased in the 1,3,7 day subgroups of IP group(P0.05,P0.01).The expression of VEGF protein and mRNA significantly increased in the rat cerebral cortex and corpus striatum in the ischemic hemisphere in the 1,3,7 day subgroups of IP group.The expression of MVD significantly increased in the 3,7 day subgroups.② In the IP group,there were no significant differences in neurologic deficit scores among subgroups,infarct volume significantly decreased in the 1,3,7 day subgroups(P0.05).The expression of MVD at 7 days,VEGF mRNA at 1,3,7 days significantly increased compared with the other groups(P0.05).Conclusion: Increased expression of VEGF and MVD induced by IP might contribute to brain ischemic tolerance.