Cerebral Ischemic Tolerance In Rat Vegf And Ang-1 Expression And Angiogenesis In Experimental Research,

To establish and evaluate a model of cerebral ischemic tolerance induced by focal ischemic preconditioning in rats.A total of 99 healthy, male, Wistar rats were randomly assigned to three groups:sham surgery (n=9), non-ischemic preconditioning (NIP, n=45), and ischemic preconditioning (IP, n=45). For ischemic preconditioning, the rats were given middle cerebral atery occlusion for 10 minutes. In the IP group, rat models of pre-ischemia-reperfusion-ischemia-reperfusion were established by occluding middle cerebral artery using the twice suture method. In the NIP group, pre-ischemia was replaced by sham surgery. Subsequently, the ischemic preconditioning and non-ischemic preconditioning groups were equally divided into five subgroups according to time of first reperfusion, including 1-,3-,7-,14-, and 21-day subgroups. The sham surgery group received the sham surgery twice. The models were evaluated with examinating neurologic deficit scores, infarct volume and nerve cell apoptosis.(1) Intergroup comparison:compared with the NIP group, neurologic deficit scores and infarct volume significantly decreased in the 1,3,7d subgroups of IP group (p<0.05; p< 0.01). The number of apoptotic cells significantly decreased in the 1,3,7 and 14d subgroups of IP group (P<0.05)(2) In the IP group, there were no significant difference in neurologic deficit scores among sugroups, infarct volume significantly decreased in the 1,3,7d subgroups (P< 0.05), the number of apoptotic cells significantly decreased in the 3,7d subgroups (P< 0.05).The results showed that 10-minute pre-ischemia induces cerebral ischemic tolerance to a subsequent severe ischemic insult, the effect of which is still present after 7 days of reperfusion. It is practicable for preparation of a rat model of ischemic tolerance induced by focal ischemic preconditioning.To investigate the mechanism of angiogenesis and expression of vascular endothelial growth factor and angiopoietin-1 in rat model of cerebral ischemic tolerance.A total of 55 healthy, male, Wistar rats were randomly assigned to three groups: sham surgery (n=5), non-ischemic preconditioning (NIP, n=25), and ischemic preconditioning (IP, n=25). For ischemic preconditioning, the rats were given middle cerebral atery occlusion for 10 minutes. In the IP group, rat models of pre-ischemia-reperfusion-ischemia-reperfusion were established by occluding middle cerebral artery using the twice suture method. In the NIP group, pre-ischemia was replaced by sham surgery. Subsequently, the ischemic preconditioning and non-ischemic preconditioning groups were equally divided into five subgroups according to time of first reperfusion, including 1-,3-,7-,14-, and 21-day subgroups. The sham surgery group received the sham surgery twice. The expression of CD34, VEGF, Ang-1 and Tie-2 protein were determined by immunohistochemical staining, and the expression of VEGF,Ang-1 and Tie-2mRNA were determined by in situ hybridization.(1)Intergroup comparison:compared with the NIP group, microvascular density and Ang-1mRNA expression significantly increased in the rat cerebral cortex and corpus striatum in the ischemic hemisphere at 3,7 days following reperfusion in the ischemic preconditioning group; the expression of VEGF, Tie-2 protein and mRNA at 1,3,7 days, as well as the expression of Ang-1 protein at 7 days significantly increased.(2) In the IP group, microvascular density at 7 days, the expression of VEGF, Tie-2 at 3,7 days, as well as Ang-1mRNA at 7 days significantly increased compared with other groups.Ischemic preconditioning upregulates the expression of VEGF and Ang-1/Tie-2, increases the microvascular density and inhibits neuronal apoptosis, which could contribute to brain ischemic tolerance.