Effects Of Gamma Knife On Cognitive Function And Toll-like Receptor4Expression In Hippocampus Of Temporal Lobe Epilepsy Rats

Objective:To analyze the effects of gamma knife radio surgery (GKS) on epilepsy and cognitive function and Toll-like receptor4expression in hippocampus of epileptic rats induced by lithium-pilocarpine. to explore its role in the development of epilepsy.Method:70healthy adult SD male rats were randomly divided into3:①A:the normal group (n=10),②B:the epilepsy group (n=10),③C:the gamma knife radiosurgery group (n=40). Epilepsy group was induced by lithium-pilocarpine. Gamma knife irradiation was performed on bilateral hippocampus of rats with a maximum dose of30Gy and50Gy.After irradiation,the changes of the seizure,behavior were observe and recorded.On the7th and28th day after irradiation.the Morris water maze were used to evaluate the ability of learning and memory of three groups.Then, Total protein was extracted from hippocampus and rat brain slices were obtained. Using Western Blot technique for detection of total protein and immunohistochemical technique for detection of the expression of TLR4in the hippocampus.Result:1.After irradiation,seizures were markedly reduced in rats of30Gy and50Gy group(P<0.05).A significant reduction was noted after50Gy irradiation in weeks3(P<0.05).After30Gy irradiation,a significant reduction was found after4weeks (P<0.05).2.Compared with control group,the Morris water maze test showed that the escape latency and the swimming distance increased significantly(P<0.05),and the number of platform crossings and the percentage of swimming time in platform quadrant decreased obviously in rats of epilepsy group(P<0.05).It showed that the abilities of learning and memory of epilepsy rats were abviously impaired.There were no significant differences in Morris water maze test between the epilepsy group and the gamma knife radiosurgery group(P>0.05).3, Using immunohistochemistry to study the expression of TLR4protein in hippocampus. TLR4protein expressed mainly in the cytoplasm of hippocampal pyramidal cells and showed brown particles. Compared with normal group,the TLR4proteins expeession in CA3area in hippocampus of the epilepsy group increased significantly(P<0.05). Compared with eplilepsy group, the TLR4proteins expeession in CA3area in hippocampus of the gamma knife radiosurgery group reduced significantly,,and the reduce number was dose-and time-related (P<0.05)TLR4protein in the hippocampus was detected in normal control group and epilepsy group and respectively using Western Blot experiments. The results showed: the gray values of TLR4protein expression in the normal group and the epilepsy group had significant difference(P<0.05).The gamma knife radiosurgery group and the epilepsy group had significant difference(P<0.05),and the reduce number was dose-and time-related.Conclusion:1.Systemic treatment of lithium-pretreated rats with several low doses of pilocarpine may be an ideal model for studying human temportal lobe epilepsy.2.In lithium-pilocarpine induced epileptic rats model,30Gy and50Gy GKS can limit seizure, and the control of seizure was dose-and time-related. During the Morris water maze test,the epileptic rats show behavioral impairment significantly After irradiation,the learning and memory ability of rats did not worse.3. Compared with normal controls, TLR4protein expression was significant increased in the hippocampus of the epilepsy group. After irradiation, TLR4protein expression was descreased. significantly,and the reduce number was dose-and time-related It imply that TLR4maybe play an important role in the development of epilepsy and Gamma Knife treatment of temporal lobe epilepsy.