The ERK Pathway And Neuroprotection Of Propofol Postconditioning In Rats

Objective Reflection of propofol postconditioning on spatial learning and memory after cerebral ischemia-reperfusion injury in rats,and the relations between propofol postconditioning and the ERK pathway.Methods 1.Creating rat focal cerebral ischemia reperfusion model established with suture emboli method(MCAO). the rats were randomly divided into four groups(n=40).Sham group(SH):neck incision to separate the left common carotid artery only;Ischemia-reperfusion group(I/R):that is MCAO model;Propofol postconditioning group(Pro); Intracerebroventricular administration of PD98059 and propofol postconditioning group(PD).30 min before the model (or sham surgery) were established all groups recept one intracerebroventricular administration of PD98059 or DMSO solution.Propofol or NS were Intraperitoneal injected at the immediate reperfusion. Neurological scoring and Infarct volume were observed after 24h of reperfusion,also the damage of hippocampal neurons were observed by HE staining. ERK phosphorylation(p-ERK) and Fos of hippocampal CA3 area were detected by immunohistochemistry.ERK1 mRNA and ERK2 mRNA of hippocampal were detected by RT-PCR.Spatial learning and memory of rats were tested by Morris water maze after 7 days of reperfusion.Results 1. HE staining showed:Hippocampal pyramidal cells of SH group were layered distribution,the cells arranged in neat, nucleolus and nuclear membrane were clear;The pyramidal cells layers of hippocampal were decreased in I/R group,cells arranged in disorder, the phenomenon of nuclear condensation and cytoplasmic concentration were more obvious, the shapes of cells were polygonal or very irregular, internal organizational structure of cells were not clear; Hippocampal pyramidal cells of Pro group were more orderly than I/R group,number of cells were more than I/R group, the phenomenon of nuclear condensation and cytoplasmic concentration were improved;PD group was similar with I/R group. 2.No Symptoms of neurological deficit and Infarct volume were detected in SH group; Neurological deficit score and infarct volume of Pro group were less than I/R and PD group,the difference was significant(P<0.05);there was no significant difference between I/R and PD group(P>0.05);3. There is a little ERK1/2mRNA expression of hippocampus in SH group;No significant difference were detected in the remaining three groups(P<0.05).4. The expression level of p-ERK1/2 and Fos in SSH group was the lowest in all groups (P<0.05); The expression of Pro group was significantly increased than I/R and PD groups(P<0.05);there in no significantly difference between I/R and PD groups(P>0.05);There was a positively correlated relationship between the expression of p-ERK1/2 and c-fos(r=0.992, P<0.05).5.Morris water maze:â‘ . Directional navigation test: Average escape latency of all groups showed a decreasing trend; Average escape latency of Pro group increased obviously compared to that of SH group,and it increased further in I/R and PD group(P<0.05);â‘¡. Space exploration experiments: The target quadrant activity time and the number of cross platform of Pro group were decreased obviously compared to that of SH group,and it decreased further in I/R and PD group(P<0.05);There was no significant difference between I/R and PD group(P>0.05).Conclusions 1.The neurons damage of hippocampal after cerebral ischemia- reperfusion injury was mitigated through propofol postconditioning,so was the ability of spatial learning and memory.2.The expression of Immediate early gene c-fos can be stimulated by propofol post- conditioning through the activation of ERK1/2 pathway,so that the damage of neurons after cerebral ischemia-reperfusion can be repaired,which may be one of the mechanisms of brain protection of propofol postconditioning.