癫痫是神经系统最常见疾病之一，以异常过度放电引发的短暂大脑功能障碍为特征。兴奋性和抑制性神经递质失衡是导致癫痫发作的生化基础，但精确调控的分子机制尚不明确；并且临床癫痫治疗药物副作用大且存在耐药现象。因此，更深入地开展机制研究，寻找有效、安全的药物新靶标是目前癫痫研究领域亟待解决的医学问题。本申请项目以血管内皮细胞CDK5信号为关键分子事件，以脑微血管内皮细胞-星形胶质细胞-神经元网络变化为主轴，开展以下研究：（1）阐明脑微血管内皮细胞CDK5信号缺失与癫痫的关联性；（2）多角度解析癫痫病灶区脑微血管内皮细胞CDK5信号与神经血管单元其他组分间通讯调控规律及机制；（3）针对脑微血管内皮细胞CDK5信号分子事件，考察药理学干预是否可有效控制癫痫发生发展的病理过程，并发现潜在药物靶标。本项目将为揭示脑血管源性信号网络在癫痫病理进程中的调控模式提供实验依据，为癫痫的治疗提供药物新靶标及候选药。

Epilepsy is one of the most common brain diseases and is characterized by a lasting predisposition to generate spontaneous epileptic seizures and has numerous neurobiological consequences. The imbalance between excitatory and inhibitory neurotransmitters is the biochemical basis for seizures. However, understanding the molecular mechanisms in epilepsy is far from clear and more effective treatment options for epilepsy remains to be developed. In this project, cerebrovascular endothelial CDK5 signaling was taken as the key molecular event, and the following hypotheses regarding the discovery of mechanisms of epilepsy have been set forth in this study. (1) To elucidate the correlation between deficit of CDK5 signal and pathological process of epilepsy; (2) To investigate potential mechanisms of endothelial CDK5 deficit induced intercellular communication disorder among cellular components of the neurovascular unit; (3) To explore whether pharmacological interventions targeting CDK5-related signal can effectively control the pathogenesis of epileptogenesis. This project will provide an experimental basis for revealing the regulation mode of cerebrovascular signaling network in the pathological process of epilepsy, and provide novel targets and drug candidates for the treatment of epilepsy.