Apoptotic Study In The Patients With Temporal Lobe Epilepsy Characterized By Hippocampal Sclerosis

Objective:Temporal lobe epilepsy(TLE ) , a main type of the focal epilepsy,has the most commen pathology of hippocampal sclerosis characterezed by preferential neuronal loss with secondary astroglial proliferation. Studies on experimental models and patients with intractable epilepsy suggest the apoptosis involving in the neural loss of hippocampi induced by reccurent seizures.This study is to search the evidence for apoptotic cell death in hippocampus of TLE patients and its potential mechanism.Method:This study was performed on Hippocampus from 27 TLE patients, who underwent surgery for drug-refractory mesial TLE in epilepsy units of West china hospital between 2002 and 2006,Only specimens that were histopathologically diagnosed as hippocampal sclerosis were selected.controls were those sufferring from trauma.Charecteristic morphology was observed by HE stain,DNA fragmentation was detected by TUNNEL and expression of Bcl-2, Bax, caspase-8, caspase-9 by immunobloting.Those apoptotic evidence was studied and the possible mechanism was explored.Result:1 Characteristic apoptotic morphologic change was neither seen in sclerotic hippocampi nor in hippocampus in control.2 In some of the TLE patients, DNA fragment was detected. the rate of apoptosis in TLE patients and control was 18.81±0.15,18.88±0.09 respectively,there is no significant deviation between them (P>0.05) ; those hippocampus from TLE patients was devided into two groups (the frequency of epilepsy more than five times per month), the rate of apoptosis was 18.81±0.05,18.97±0.04 respectively, there is significant deviation (P<0.01) . there is significant deviation between the group with more than five times per month and the control (P<0.01) ,while there is no significant deviation between those with less than five times per month and the control (P>0.05 ) .3 Bcl-2,Bax,caspase-8,caspase-9 were up-regulated.The ratio of OD between Bcl-2 and P-actin was 0.899±0.006 in sclerotic hippocampi, 0.455±0.004 in control; the ratio of bax and p-actin was 1.008±0.005 in sclerotic hippocampi, 0.582±0.004 in control; the ratio of caspase-8 and p-actin were 0.4370±004, 0.280±0.012 respectively in TLE patients and control; the ratio of caspase-9 and p-actin were 0.4380±004,0.254±0.007 respectively.The ratios were significantly different between TLE patients and control.Conclusion:1 Cell apoptosis exists in the hippocampus of TLE patients.2 extrinsic pathway and Intrinsic pathway may be involved in the mechanism of caspase activation.