The Expression Changes Of TDP-43 After Cerebral Ischemia In Rats And The Mechanism Of Regulation By Ginsenoside Rg1

Objectives:1.To observe the changes of TDP-43 in the cortical region of rats after cerebral ischemia,and to explore the pathological changes and mechanism after cerebral ischemia;2.To explore the effect and mechanism of ginsenoside Rgl on TDP-43 after cerebral ischemia,and to provide theoretical basis for prevention and treatment of cerebral ischemia.Methods:In this study,A total of 96 adult SD male rats was randomly assigned to 4 groups:Sham group,MCAO group,NS group,and Rg1 group.At each of after completion of MCAO each group was further divided into three different time points(3d,7d,14d)after MCAO(n=4).After neurological function and head MRI measurement,rats were perfused at the corresponding time points.The brain tissues in the ischemic cortex were collected and the protein changes of TDP-43,p-ERK,p-JNK and p-p38 were detected by Western blot.The mRNA level of TDP-43 was detected by QPCR.The changes of TDP-43 were observed by immunohistochemical staining.IBM SPSS Statistics 25 was used to conduct one-way ANOVA and pair comparison of the data,and P<0.05 was considered statistically significant.Results:1.Bederson neurological deficit score showed that the MCAO group had the obvious neurological deficit and the Rg1 group got bettter neurological function recovery.Cranial magnetic resonance imaging(T2WI)showed significant hyperintensity shadow and brain swelling in the MCAO group,but less in the Rg1 group than in the NS group.2.The changes of TDP-43 in the ischemic cortex after cerebral ischemia were detected by Western blot,immunohistochemical staining and QPCR as follows:Compared with the Sham group,the expression of TDP-43 in the MCAO group and the NS group was significantly increased at each time point,with statistical significance(P<0.05).Compared with the NS group,the expression of TDP-43 in the Rg1 group was decreased at each time point,with statistical significance(P<0.05).3.The changes of p-ERK were as follows:the result of Western blot showed that compared with Sham group,p-ERK protein expression in the MCAO group and NS group was decreased at each time point(P<0.05).Compared with the NS group,p-ERK expression was increased in the Rg1 group,with statistical significance(P<0.05).4.The changes of p-JNK were as follows:Western blot showed that compared with Sham group,p-JNK protein expression in MCAO group and NS group was elevated at each time point,with statistical significance(P<0.05).Compared with NS group,p-JNK expression was decreased in Rg1 group,with statistical significance(P<0.05).5.The changes of p-p38 were as follows:Western blot showed that compared with Sham group,p-p38 protein expression in the MCAO group and NS group was significantly increased at each time point(P<0.05).Compared with the NS group,the expression of p-p38 in the Rg1 group was significantly decreased,with statistical significance(P<0.05).Conclusions:1.The neurologic dysfunction is closely related to the overexpression of TDP-43 following cerebral ischemia in rats.2.Ginsenoside Rg1 may attenuate the neurodegeneration and neurological dysfunction caused by cerebral ischemia through down-regulation of TDP-43.3.Ginsenoside Rg1 may reduce the overexpression of TDP-43 after cerebral ischemia through the MAPK signaling pathway.