癫痫是神经系统常见疾病之一，其治疗手段主要为药物或手术治疗，但只对约70%患者有效。目前普遍认同的观点是神经网络中兴奋和抑制间的不平衡引起了癫痫发作，而现有的治疗主要靶向神经元，对脑细胞外微环境病变引起的癫痫发作尚无关注也无有效干预手段。本课题首先通过构建微环境病变癫痫模型：胶质细胞整合素β1基因敲除模型、胶质瘤旁癫痫模型，以及微环境非特异性病变癫痫模型-铁离子模拟脑出血后癫痫模型，应用不同手段（广视野成像技术，Video-EEG监测等），比较不同癫痫模型中脑细胞外微环境变化与癫痫的关系；再应用对流增强给药（CED）技术置换脑脊液以恢复脑细胞外微环境，验证恢复脑细胞外微环境可以控制癫痫发作；最后我们将应用免疫组化、WB等技术在细胞、分子层面探索该脑细胞外微环境恢复方法控制癫痫发作的潜在机制。总之，本课题将通过调控脑细胞外微环境达到控制癫痫发作的目的，为探索难治性癫痫新疗法提供理论基础。

Epilepsy is one of the most common diseases in neurology department. At present the commonly used means of epilepsy treatment is drug therapy or surgical treatment, but only about 70% of the patients are effective. At present, it is generally accepted that the imbalance between excitatory and inhibitory activities in neural networks causes seizures, and the current treatment methods are mainly targeted at neurons. No attention has been paid to epilepsy caused by microenvironmental dysfunction and no effective treatment has been found. Therefore, in this project，we will construct three epileptic models at first, including two models of microenvironmental lesions (glial integrin β 1 gene knockout model and para-glioma epilepsy model) and a model of non-specific microenvironmental lesions(iron mimics epilepsy models after intracerebral hemorrhage).Secondly, by different methods, such as wide-field imaging, Video-EEG, etc., the relationship between the changes of cerebral extracellular microenvironment and seizure in different epilepsy models will be compared. Meanwhile, convection-enhanced delivery(CED) technique will replace cerebrospinal fluid by artificial cerebrospinal fluid(ACSF) to restore the cerebral extracellular microenvironment and verify that the restoration can control seizures. Finally, we will use Western-Blot, immunohistochemistry and other techniques to explore whether the cerebral extracellular microenvironment restoration strategy can control seizures, in the cell, molecular level. In a word, this subject will control seizures by restoring cerebral extracellular microenvironment, and provide a new therapy strategy for patients with intractable epilepsy, so as to lighten the burden of patients themselves, family and society.