Treatment With The GLP-1 Analogue Liraglutide Affect The Chronic Inflammation And Mitochondrial Stress Induced By Status Epilepticus

Objective:The present study aims to investigate the effect of liraglutide on neuroinflammation and mitochondrial stress in hippocampus after lithium-pilocarpine induced SE.Methods:The 54 male SD rats were divided into three groups:(?)saline treated control group(control group)(n=6);(?)pilocarpine treated group(SE group)(n=24);(?)pilocarpine+liraglutide group(SE+LI group)(25nmol/kg/day)(n=24).The pilocarpine treated group and pilocarpine+liraglutide group would divided into four subgroups(n=6)according to the different time points(12h,1days,3days,7days)after termination of SE.We detected the inflammatory cytokines(TNF-?),actived glia marker(IBA1 and GFAP)and the mitochondrial stress marker BAX and the survival factor Bcl-2 in hippocampus by immunohischemistry and western blot.Results:1.Treatment with liraglutide(25nmol/ kg.ip.)once-daily for 7 days inhibits the activation of glia as shown by reduced level of IBA1 and GFAP.Compared to the SE group,the GFAP level in DG area of SE+LI group was reduced(p<0.001)after 12 hours,and after 1 day the GFAP level in CA3 region of SE+LI group was lower than SE group(p<0.05),after 3 days the expression of GFAP in CA1 region of SE+LI group is decreased(P<0.001)and has no difference with the SE group(p>0.05).1 day after the termination of SE,the GFAP level in CA3 and DG regions in SE+LI group is equal to SE group(P>0.05).Compare to the SE group,3 days after the termination of SE,the expression of IBA1 in CA1,CA3,DG areas of SE+LI group is reduced(p<0.01),and the IBA1 level has no statistical difference with the control group after 7days(p>0.05).The results from western blot is also present the inhibition of liraglutide on IBA1 expression and GFAP expression.2.Compare to the SE group,the expression of BCL2 in CA3 area of SE+LI group increased at the termination of 12 h(P<0.05),1d(P<0.01)and 3d(P<0.05)after SE,but after 7days the BCL2 expression had no difference with the SE group(P>0.05);1day after the termination of SE the level of BCL2 raised in DG areas of SE+LI group(P<0.05),but after 3 days the BCL2 level had no statistical difference with the control group(P>0.05).Compare to the SE group,the expression of BAX decreased after 12 h in DG area(P<0.01)and 1d in CA3 area(P<0.01)of SE+LI group;3 days after termination of SE the BAX level in CA1 area,DG area and CA3 area of SE+LI group were higher than the control group(P<0.05).3.Compare to the SE group,12 hours and 1 day after the termination of SE,the expression of TNF-? was lower in the SE+LI group,but has no statistical difference(P>0.05);After 3 days,the TNF-? level in SE+LI group has a great difference with the SE group(P<0.001).Conclusion:GLP-1 analogue Liraglutide have protective effects in the brain after SE through alleviating the chronic inflammation and mitochondrial stress in hippocampus.