反应性Astrocytes增生是颞叶癫痫（TLE）海马硬化的主要病理特征。临床上应用外科手术切除TLE患者部分病变的海马，但疗效甚微。近年研究发现癫痫发作中反应性Astrocytes异常增生，常伴有离子通道的开放和信号通路的激活，且能够触发癫痫病灶内神经元超同步化放电，其具体机制不明。我们前期研究证实Wnt/beta-catenin通路在海马神经发生中具有重要作用。预实验结果发现Wnt信号分子在癫痫病灶内表达增高，提示其可能参与癫痫发生。本项目拟在细胞水平，动物整体和组织脑片多个水平上，结合基因转染、EEG脑电监测和CoIP免疫共沉淀等技术手段，系统研究癫痫发生中Ascl1调控 Wnt/beta-catenin的作用及分子机制。通过该研究，我们试图探索癫痫发作中靶向干预反应性Astrocytes异常增生转分化为功能性神经元的新策略，为实现海马硬化的重塑，提供重要的实验依据。

Reactive astrogliosis is the main pathological changes in hippocampal sclerosis of Temporal lobe epilepsy (TLE). In clinic, the part of hippocampal sclerosis was often removed by surgery, but which was no much better treatment effect. Although recently studies revealed that the reactive astrogliosis, accompanied by the opening of ion channels and activation of signaling molecules on astrocytes, those can trigger super synchronization of neurons discharge, how they lead to epileptogenesis still remains unknown.Our previous studies have shown that wnt/beta-catenin signaling pathway plays an important role in hippocampal neurogenesis. Preliminary experimental results also found the expression of Wnts signaling molecules was increased significantly in hippocampi of epileptic rats, which indicates the activated Wnt/beta-catenin signaling pathway could involve and aggravate in epileptogenesis. Our present study is intend to comprehensively study the role of Ascl1-regulated wnt/beta-catenin signaling pathway and its molecular mechinism in epileptogenesis via gene transduction, EEG monitoring and CoIP techniques coupling with cell culture, animal model and brain slices.We attempt to discover the novel strategy of targeting intervention reactive astrogliosis for seizures and provide the key theoretical evidence for reconstructing hippocampal sclerosis.