脑出血后局部γ-氨基丁酸受体的变化及对癫痫的作用研究

Intracerebral hemorrhage（ICH）is one of the most severe central nervous system diseases, accounts for 15% of human death, usually accompanied with complications. Epilepsy is one of the most common complications after ICH severely impacting the quality of your life, with the incidence of 2.7%-17%. Iron is considered as an important factor causes epilepsy after ICH. The primary mechanism is related to the free radical released from the oxidation-reduction reaction. However, the changes of neuron, neural transmitters and receptors affected by iron are still not clear. GABA receptors are the main inhibitory receptors on the neuron membrane, which can suppressed the neuron activities. However, these receptors were found up regulated in some chronic epilepsy. Similar with our findings, we also demonstrated the over expression of GABA receptors in an iron-induced epilepsy rat model. Thus, we hypothesis that the abnormal imbalance of the excitatory/inhibitory efficiency may contribute to the epileptogenesis. In this study, we plan to reveal the relationship among iron concentration, epilepsy degree and excitatory/inhibitory efficiency, and then adjust the excitatory/inhibitory receptors to record the epilepsy mode. Our objective is to provide a basis for epilepsy treatment after ICH.

脑出血（ICH）是一种严重的神经系统疾病。癫痫是ICH后的一类常见并发症，发生率为2.7%-17%，是ICH治疗过程中不能忽视的重要环节。一般认为，癫痫发作是由于局部兴奋性效能增高和抑制性效能降低有关，但有时抑制性效能却会出现反常升高现象。γ-氨基丁酸（GABA）是脑内重要的抑制性神经递质，GABA能神经元的活跃能够抑制脑内神经元的电活动，但在我们前期的FeCl3诱发大鼠慢性癫痫实验中， GABA效能却出现上调。对此我们猜测，ICH后局部抑制能升高现象是导致癫痫发作的可能机制，有待进一步探究。据此，本项目将首先建立铁离子诱发癫痫大鼠模型，模拟ICH后癫痫，明确铁离子浓度-癫痫发作程度-抑制性效能三者的变化关系；然后通过在大鼠局部皮层内调节神经递质受体，构建局部GABA能升高的大鼠模型，观察癫痫发作情况；最后通过反向治疗尝试控制铁离子诱发癫痫大鼠的症状，为该病的临床治疗提供依据。