Changes of mossy fiber sprouting and P-glycoprotein expression in the hippocampus of rat models of amygdala-kindling epilepsy

Abstract

Objective To explore the relationship between plasticity ofhippocampus neuronal morphology and pathogenesis of epilepsy by observing the changes of mossy fiber sprouting (MFS) and P-glycoprotein (P-gp) expression in the hippoeampus of rat models of amygdala-kindling epilepsy.Methods Ninety male Wistar rats were randomly divided into epilepsy model group (n=40),drug treatment group (n=40) and sham-operated group (n=10).Models of chronic epilepsy were established by stimulating the amygdale; rats in the drug treatment group were perfused antiepileptic drug levetiracetam into stomach [100 mg/(kg·d),twice daily].At different observation time points (1,2,4 and 8 weeks after the treatment),Timm staining was employed to observe the changes of MFS; immunohistochemical method was used to detect the dynamic changes of P-gp.Results (1) After the success of model making,abnormal MFS levels in the hippocampal CA3 transparent layer were noted; lowest MFS scores were noted in S1 subgroup,which showed no significant difference as compared with those in sham-operated group (P＞0.05); the MFS scores in S2,S4 and S8 subgroups increased gradually with a peak level at 8 weeks after inducement,which showed significant difference as compared with those in sham-operated group (P＜0.05).No significant differences on MFS grading scores were noted in the drug treatment group between each two time points (P＞0.05).(2) The P-gp expression in the epilepsy model group showed significant difference at different time points (P＜0.05); highest expression level was noted at one week after the surgery,and returned to normal at four weeks.However,the P-gp expression showed no significant difference in the drug treatment group between each two time points (P＞0.05),except for 1 week after treatment.Conclusion MFS is the important mechanism of chronic epilepsy,and P-gp is the product of epilepsy,which is the main reason of epilepsy drug resistance. Key words: Mossy fiber sprouting; P-glycoprotein; Epilepsy; Levetiracetam