Curcumin Has Antiepileptic Effect By Inhibiting P-MTORC1 Activity In The Brain Of Posttraumatic Epilepsy Rats

Objective:Curcumin is a kind of polyphenol compounds with multiple nerve protective effect and also show some Antiepileptic effect for traumatic epilepsy, but the underlying mechanismof antiepileptic action is still controversial.In recent years, A large number of studies had shown that the abnormal activation of mammals rapamycin target protein complexes 1 signaling pathway had close relation with traumatic epilepsy, and participated in the development of epilepsy.In this paper, we established the traumatic epilepsy rat model by iron injection in rat cortices,and to investigate the antiepileptic effect of curcumin and the effect on the expression levels of the mammalian target of rapamycin complex 1 (mTORC1) in the post-traumatic epilepsy rats.Methods:120 SD rats were randomly divided into three groups: control group, model group and intervention group, The rat models of epilepsy were established by iron injection in rat cortices in the latter two groups, and the animals of the control group were administered with an intracortical injection of equal saline. The rats of intervention groups received an intraperitoneal injection of curcumin 1 hour before modeling and received continuous use for 14 days. Rats in each group were randomly selected at each time points(6h,24h,3d,7d,14d)after epileptic seizure.Racine scale was used to evaluate the behavioral changes,Cortical electroencephalogram(EEG) monitoring was applied to record the EEG features, Transmission electron microscope was used to evaluate the neurons in the injection lateral cortex,Western blotting were applied to measure the protein expressions of mTORC1 and the degree of phosphorylation (p-mTORCl), and also the p-mTORC1 was detected by immunohistochemistry.Results:Typical seizures and epileptic discharge w were observed in the model and intervention group, the frequency and degree of epileptic seizure of rats from intervention group were less obvious than those of model groups(P< 0.05),and the epileptic discharge and amplitude of the epileptic wave were much lower(P<0.05) in the intervention group than those in the model group at each time point. In cortical cells of the model group rats, subcellular structures of neurons were degeneration and death, in contrast, Curcumin-treated epileptic rats exhibited normal subcellular structures. The mTORC1 was phosphorylation activated obviously in the model group, observerd through both the Western blot and immunohistochemistry.The degree of activation was obviously higher than those in the normal group at each time point(P<0.05), and peaked at 24h following injection of FeCl3, and in the curcumin intervention group were significantly lower than these in the model group(P<0.05).Conclusions:Curcumin may had a certain antiepileptic effect by inhibiting the expression of p-mTORC1 and its mediated signaling pathways in iron-induced post-traumatic epilepsy rats.