Effect Of Ischemic Preconditioning On Expression Of VEGF,MMP-9 And MVD After Focal Cerebral Infarction In Rat

Background and objectives : Brain ischemic tolerance ( IT ) is the phenomenon whereby a preconditioning ischemia of brief duration, inadequate to infarct the brain, protects it from subsequent severe ischemia. However, the molecular mechanisms underlying IT of brain remain incompletely understood. The present experiment was conducted to explore whether ischemic preconditioning(IP) can alter MVD which was assessed with CD34 immunohistochemistry ,MMP-9 and VEGF immunoreactivities from cell morphology.Methods:114 SPF healthy adult male adult Wistar rats were randomly divided into experimental group, control group, sham-operated group and normal group. Transient MCAO(15 min) was used for IP. 48h reperfusion was allowed after IP and before PMCAO to establish IT. VEGF,MMP-9 and CD34 expression 24h after PMCAO were determined and compared with control group and shame-operated group respectedly. The neurological deficits, brain water content and the histological findings with HE staining were also examined.Results : IP significantly reduced neurological deficits after PMCAO, meanwhile brain water content in the ischemic hemisphere was significantly reduced and the brain edema was alleviated by IP. The histological injury in IP experiment groups were mild. Immunohistochemical examination revealed that MMP-9 immunoreactivities in IP experiment groups 24h after PMCAO were lower than that in control group or sham-operated group. VEGF and microvessel density expression significantly increased compared to control group or sham-operated group. There were no significant difference between control group and sham-operated group. The MVD in IP experiment groups had a significant difference compared to control group, There were no significant difference of MVD among control group and sham-operated group.Conclusion:IP provided significant brain protection to subsequent PMCAO. There were significantly lower expression of MMP-9 in ischemic penumbra in IP rats with higher expression of VEGF and microvessel density immunoreactivities after PMCAO. It suggest that IP might induced IT in brain so that reduced MMP-9, increased VEGF and microvessel density. Ischemic preconditioning induced ischemic tolerance and provided protective effects on rat brain microvascular endothelial and neuronal survival.