Time-dependent contribution of cerebral ischemic tolerance induced by ischemic preconditioning in rats

Objective To investigate the ischemic tolerance induced by ischemic preconditioning(IP) in difference time intervals in rats.Methods IP was induced by intraluminal filaments in middle cerebral artery for 10 min.Middle cerebral artery occlusion(MCAO) was induced by intraluminal filaments on the different time points of 6 h,24 h,3 d,7 d and 14 d post IP and continued for 2 hours.110 SD rats were randomly divided into 2 groups: The SS+MCAO group only received 2 h MCAO followed by 22 h reperfusion with pretreatment of sham surgery,focal IP group(IP+MCAO) received 2 h MCAO followed by 22 h reperfusion with pretreatment of IP.At the end point of 22 h perfusion,the infarct volume,histopathological changes,the expressions of glial fibrillary acidic protein(GFAP) and brain-derived neurotrophic factor(BDNF) by using immunohistochemistry method were evaluated in each group.Results The infarct volume in IP+MCAO group(24 h,3 d,7 d,14 d) were significantly less than that in SS+MCAO group(P0.05),and within 6 h the infarction volume was comparable between these two groups.The brain pathological changes were more pronounced in IP+MCAO group than in the SS+MCAO group.The numbers of GFAP and BDNF positive cells in the brain in the 3 d/7 d subgroups of IP+MCAO were significantly more than those in the SS+MCAO group(P0.05).The GFAP expression in the SS + MCAO group was few,increased in each group of IP + MCAO,and the increase was more in the 3 d and 7 d subgroup of IP + MCAO(P0.05).BNDF expression was detectable at 6 h after ischemia,became maximum 3 d and 7 d,and began to decrease 14 d post IP.Conclusions IP not only caused damages to the nervous system,but also produced ischemic tolerance;ischemic tolerance occurred in 24 h,3 d,7 d,14 d post IP,and showed the strongest protective effects in brain in 3-7 d.The BDNF expression and the protective effects of ischemic tolerance were in the similar time courses,suggesting that BDNF may be one of the important mechanisms for ischemic tolerance.