创伤性脑损伤(traumatic brain injury, TBI)是导致人类残疾和死亡的重要原因之一。TBI后癫痫会加重TBI的症状，严重影响TBI的恢复。星形胶质细胞是引发癫痫的主要原因，也是TGF-β等细胞活性因子的主要来源和作用靶点。可是人们对于TBI后，TGF-β等细胞活性因子和星形胶质细胞功能障碍诱发癫痫的作用机理依旧不明确。本课题将对TBI如何诱发癫痫的机理进行探讨。我们将利用组织化学和电生理技术，试图解决以下三个问题：1.星形胶质细胞释放 TGF-β 等对 TBI 诱发神经元 NKCC1 表达的影响 ；2.TBI 后大脑皮层神经元中 NKCC1 表达的改变所引起的小鼠行为学和 脑电的改变；3. NKCC1敲除和抗NKCC1药物对TBI后早期癫痫的影响。本课题将对阐明TBI诱发癫痫的机制有重要意义，并为TBI的治疗提供新的思路。

Traumatic brain injury (TBI) is the leading cause for morbidity and mortality worldwide, especially for children. TBI is also a leading cause for seizures. Early posttraumatic seizures in turn are a contributing factor to ongoing acute damage. It is critically important to control the early seizure for TBI patients. Most of the antiepileptic drugs used are targeted at gamma-aminobutyric acid (GABAA) receptors. But the inhibitory activity of GABAA depends on low intracellular Cl-, which is achieved by the opposite regulation of Na+- K+-Cl- cotransporter 1 (NKCC1) and K+-Cl--cotransporter 2 (KCC2). Up-regulation of NKCC1 in neurons has been proved to be involved in neonate seizure. We also reported that up-regulation of NKCC1 was involved in ammonia toxicity induced seizure. Here we hypothesized that up-regulation of NKCC1 might be the reason for TBI induced seizures, as can explain the reason for high incidence of seizure in TBI children. .In this project, we will probe into three mechanisms that are involved in the TBI induced early seizures. Aim1: Have the expressions of NKCC1 and KCC2 changed after TBI? We hypothesize that trauma induced up-regulation of NKCC1 and down regulation of KCC2 in cortical neurons are involved in TBI induced seizure. Aim 2: What is the mechanism for the up-regulation of NKCC1. We hypothesize that glia derived neurotropic factors are the major reasons for the up-regulation of NKCC1 in cortical neurons. Aim 3: Can the drugs that block NKCC1 cure the TBI induced seizure? In all, we hope that we can identify neuronal up-regulation of NKCC1 as an important mechanism in early post-traumatic seizures, and demonstrate the therapeutic potential of blocking this pathway by inhibiting NKCC1.