海马电刺激对耐药性颞叶癫痫大鼠脑细胞GABA（A)受体及钠通道电流的影响

多项实验研究以及临床试验表明海马电刺激对颞叶耐药性癫痫有治疗作用，耐药性癫痫患者脑组织中GABA及其受体减少，而进行海马电刺激后可见GABA含量增加，但目前尚不清楚海马电刺激是否通过增加GABA系统的功能而发挥治疗耐药性颞叶癫痫的作用。本研究拟建立耐药性颞叶癫痫大鼠模型，以自发性及诱发性癫痫发作、杏仁核后放电为指标，观察进行病灶侧海马亚急性电刺激治疗并观察海马电刺激的疗效，与此同时检测海马细胞外液GABA浓度及海马细胞GABA受体的标的情况，探讨GABA系统在海马电刺激治疗耐药性颞叶癫痫中的作用。以耐药性癫痫大鼠海马细胞钠离子通道激活曲线、失活曲线、电流-电压曲线、失活后恢复曲线等为观察指标，探讨海马电刺激对耐药性癫痫大鼠脑细胞钠通道电流活性的影响。通过上述研究，为海马电刺激治疗耐药性癫痫的机制探讨积累资料。

Although several clinical and experimental studies suggested hippocampal stimulation to be effective in pharmacoresistant TLE, the mechanisms underlying the therapeutic effects of hippocampal stimulation in treatment of TLE remain poorly understood.In the present study,the effect of hippocampal stimulation on the spontaneous seizures and kindling stimulus-evoked seizures are observed.Hippocampal GABA content,GABA(A)receptor and the sodium chanel current in rats with phamacoresistant epilepsy are also observed,so as to investigate the mechanism of hippocampal stimulation in the treatment of pharmacoresistant epilepsy.We prepare firstly the amygdala kindling epileptic rat model,and then the pharmacoresistant epileptic rats are selected by testing their response to Phenytoin and Phenobarbital, and they are randomly divided into a hippocampal electrostimulation group A(PES group A) and a pharmacoresistant control group(PRC group).A stimulation electrode was implanted into the hippocampus of all the rats. Low frequency hippocampal stimulation was administered twice per day in the PES group for two weeks. The PRC group receive only sham stimulation.The spontaneous seizurs and stimulus-evoked seizures,as well as the amygdala afterdischarges are used as indexes to observe the effect of hippocampal stimulation.A real-time PCR and Western Blot are used to quantify the GABA(A) mRNA and its protein.A method of high performance liquid chromatography is used to measure the hippocampal GABA content after hippocampal stimulation.A whole-cell recording technique by patch-clamp was used to observe the changes of sodium current of hippocampal pyramidal neurons after the hippocampal stimulation.