The Effects Of The Electrical Stimulation Epileptic Foci On Seizure, Electroencephalogram And Mossy Fiber Sprouting In Hippocampus In The Kainic Acid-Kindled Rats.

【Object】Our aim was to establish and evaluate the temporal lobe epilepsy(TLE) rat model which kindled by kainic acid(KA),and observe the effects of the kindled rats on seizure ,electroencephalogram and mossy fiber sprouting in hippocampus by high frequency stimulation(HFS) of the hippocampal epileptic foci,and investigate the HFS mechanism.【Method】Seizures were induced in adult male SD rat and to establish the TLE rat model with unilateral intrahippocampal KA injection by stereotactic technique.With high frequency stimulation(HFS) of the hippocampal epileptic foci ,the study observe seizure characteristics in different time, the electrophysiological evidence was recorded by video frequency electroen- cephalographic monitoring, the histopathological change of hippocampus was investigated by HE staining,Nissl staining and Timm staining. smea3A and GAP-43 mRNA expression in the hippocampus were examined by real-time fluorescence quantitative reverse transcription-PCR.【Results】1. Behavior: The symptome of the rats could be divided clearly into three Phases: acute phase,the rats began local epilepsy immediately after KA injection; silent period,it was a period with no symptome after acute phase;chronic phase ,the spontaneous recurrent seizures were the character of this phase ,and existed persistently. HFS may reduce the spontaneous recurrent seizures in the chronic phase by 50.78%. 2.EEG: The acute phase could see the continuous slow wave of high amplitude of wave, sharp wave, spike wave or spike slow wave discharges; In the silent period the EEG return approximately normal ,including the little low amplitude of sharp wave,spike slow wave discharges;The main characteristic of EEG was paroxysmal spike slow wave, sharp wave discharges in the chronic phase;HFS can decrease epileptic discharges in the chronic phase by 58.05%. 3.Pathology: At 14 days following induction of SE,the hippocampal epileptic foci appeared neuronal degeneration and neuron necrosis,glial cells hyperplasia,and the sieve cencephalomalacia focus by HE staining. The hippocampal CA1 pyramidal neuronal death can be observe by Nissl staining,the number of pyramidal neuronal death in the HFS group was fewer than that in the KA group;The mossy fiber sprouting evidence was appeared at 4 days following induction of SE,and was robust at 14th day (p<0.01).HFS can prevent the mossy fiber sprouting to some extent(p<0.05).4. molecular level:In the KA group ,there were downregulation of sema3A mRNA expression(p<0.01) and upregulation of GAP-43 mRNA expression(p<0.01) in the hippocampus at 1th day after KA injection,the sema3A mRNA expression returned normal at 7th day and continued to 14th day,the GAP-43 mRNA expression was supreme in 1th day(p<0.01) ,and later gradually receded,but still maintained higher than the normal level until 14th day(p<0.01).HFS can inhibit the downregulation of sema3A expression (p<0.05),had returned normal level at 4th day and continued to 14th day,but HFS didn't affect to the GAP-43 mRNA expression(p>0.05).【Conclusion】1. Seizures were induced and to establish the rat epilepsy model with unilateral intrahippocampal kainic acid (KA) injection by stereotactic technique,the model can simulate the human temporal lobe epilepsy(TLE) feature well and is the ideal TLE model.2. HFS of the hippocampal epileptic foci can prevent epileptic seizures to some extent.3.The one of mechanisms that HFS controll seizures may be through preventing the downregulation of sema3A mRNA expression,and reducing the mossy fiber sprouting,and preventing the reconstruction of hippocampus synapse,and depressing seizure sensitivity.