不同类型脑皮层发育不良致难治性癫痫的分子基础

项目名称： 不同类型脑皮层发育不良致难治性癫痫的分子基础

项目编号： No.81471328

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张国君

作者单位： 首都医科大学

项目金额： 70万元

中文摘要： 癫痫是中枢神经系统的常见病，大脑皮层发育不良(Cortical Dysplasia, CD)是引起难治性癫痫的一个主要原因。研究证明CD组织中GABA神经元功能减弱导致CD神经网络兴奋性异常升高。本人前一个国基金研究发现：不同类型CD组织兴奋阈值不同，形态异常神经元周围PV阳性的颗粒状物质和神经元树突围绕情况不同。本项目将扩大样本量，结合电生理、形态学、免疫组化等方法精确区分CD和CD旁组织，分类研究CD中GABA能神经元功能减弱的基础：(1)记录和分析GABA能神经元放电频率，检测其产生冲动的能力是否受损；(2)分析GABA能神经元上自发兴奋性和抑制性突触后电流的幅度与频率，检测驱使该神经元兴奋的动力是否降低；(3)通过双细胞记录，测定GABA能神经元细胞膜上Kv3家族钾通道表达是否减少,以及CD组织中GABA-A和GABA-B受体表达含量的变化，为更有效治疗该疾病提供理论基础。

中文关键词： 癫痫；皮层发育不良；分子机制

英文摘要： Cortical dysplasia(CD) is the main reason of the intractable epilepsy.The recent research uncovered that the excitablity abnormally increased and excitatory neurons discharge was out of control in the CD neural networks. The key reason of the abnormal excitability increase of CD is the dysfunction of GABA neurons.we found that different types of CD has different excited threshold, abnormal shape positive neurons around the PV and neuron dendritic granular material is different. In this project we will enlarge the amount of specimen, making accurate localization of CD and its adjacent tissue. use the human CD cortex from the resection tissue from epilepsy operation to study the basic mechnism of GABA neurons dysfunction in different CD by the means of electrophysiology, immunohistochemisty, and morphology. The principle contents of this research is as follows:(1) to record and analysis the discharge frequency of GABA neurons, and detect whether the impulse-genic ability of GABA neurons is intact. (2) to analysis the frequence and amplitude of spontaneous excitatory and inhibitory post-synaptic discharge in GABA neurons, and detect whether the ability to drive the GABA neurons is decreased.(3) to detect whether the expression of the Kv3 family on the surface of GABA neurons, and the variation of the content of GABA-A receptor and GABA-B receptor in CD cortex. This study will reinforce our understanding of the principle mechnism of epilepsy genesis in different CD, and then provide the theory base for the treatment of this disease.

英文关键词： epilepsy;cortical dysplasia;molecular mechanism