ABSTRACT
Objective To assess the effect of ischemic postconditioning on the Notch1 signaling pathway,and learning and memory in rats with global cerebral ischemia.Methods A total of 128 healthy male SD rats were randomly divided into the sham operation (sham),whole-brain ischemia(CIR),ischemic treatment(CIP),and inhibitor(DAPT) groups,with 32 rats in each group.A global cerebral ischemia model was generated using the modified Pulsinelli's four-vascular occlusion model,and the inhibitor group was injected intraperitoneally with gamma secretase inhibitors (DAPT) before ischemic treatment.Rats' learning and memory function results from the Morris water maze test were assessed by observing the changes in hippocampal CA1 neurons with HE staining.The expression of Notch1 in the CA1 area of the hippocampus was assessed using immunohistochemical and Western blotting methods in rats.Results Compared with the sham group,the hippocampal cell survival rate in the CIR group decreased significantly (P ＜ 0.05) and the expression level of Notch1 increased significantly (P ＜ 0.05).Compared with the CIR group,the CIP group revealed a significantly higher hippocampal cell survival rate (P ＜ 0.05) and an increase in Notch 1 expression (P ＜ 0.05);compared with the CIP group,the hippocampal cell survival rate significantly decreased after DAPT administration (P ＜ 0.05) and Notch1 expression decreased significantly.Conclusion Ischemic postconditioning can promote the recovery of learning and memory ability,which may relate to the activation of the Notch 1 signaling pathway.
ABSTRACT
Objective To explore the mechanism of ischemic postconditioning in relieving cerebral ischemia reperfusion (IR) by regulating autophagy through P38MAPK pathway.Methods Cerebral ischemia reperfusion model was established by using modified Pulsinelli four-vessel occlusion (4-VO).Totally 128 male SD rats were divided into 4 groups randomly:control group (sham),cerebral ischemia reperfusion model group (CIR),cerebral ischemic postconditioning group (CIP),and cerebral ischemic postconditioning + P38MAPK inhibitor group (SB203580 group).Each group was subdivided into four time points:6 h,24 h,48 h,and 72 h.The morphological changes of the hippocampus CA1 area neurons at each time point and the number of surviving nerve cells were detected with HE staining.The expression of the hippocampus CA1 area phosphorylated P38MAPK and the autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with immunohistochemistry.The protein content of the hippocampus phosphorylated P38MAPK and autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with Western blotting.Results Compared with those in sham group,the damage of rats' hippocampal neuron structure and the survival rate of neurons at each time point decreased in CIR group,the expressions of p-P38MAPK,LC3-Ⅱ and Beclin-1 increased.Compared with those in CIR group,in CIP and SB203580 groups the structure of rats hippocampal neurons was improved,the survival rate of neurons increased,the expression of p-P38MAPK decreased and the expressions of LC3-Ⅱ and Beclin-1 increased at each time point.Compared with CIP group,SB203580 grouphad improved structure of rats' hippocampal neurons,increased survival rate of neurons,decreased expression of p-P38MAPK,and increased expressions of LC3-Ⅱ and Beclin-1 at each time point.Conclusion Cerebral ischemic postconditioning through inhibiting P38MAPK pathway can regulate autophagy and exert its nerve-protective effect.