研究证实外源性神经干细胞或GABA能前体细胞对颞叶癫痫发作具有抑制作用，其确切机制尚不详，提示与分化补充GABA能中间神经元形成抑制性突触，建立新抑制性神经网络有关。前期研究显示癫痫发生致大量神经元丢失及GABA受体数量和亚基结构异常，应用HIF-1α抑制剂后神经元的丢失和海马齿状回颗粒细胞下区异常神经发生明显减少。因此我们假设：植入神经干细胞可增加GABA能中间神经元，建立新的抑制性神经网络；并提出HIF-1α抑制可限制癫痫发生中海马自身的病理发展，辅助提高外源性神经干细胞抗癫痫作用及避免新生的GABA受体的再损害。拟用研发的磁共振光学报告基因（FTH-EGFP）标记神经干细胞或GABA能前体细胞，分别在成幼年癫痫大鼠模型上研究标记的神经干细胞或GABA能前体细胞在癫痫发生或HIF-1α抑制下的结构变化和功能作用；进一步阐明神经干细胞治疗成幼年癫痫的作用机制，为治疗癫痫提供新策略。

Previous studies demonstrated neural stem cells (NSCs) or GABAergic neurons transplantation is a powerful approach to restrain seizures, while the precise mechanisms underlying cell transplantation strategies mediated seizure suppression are yet to be clear known. The promise of cell transplantation therapy for restraining spontaneous recurrent seizures (SRSs）in TLE may stem from their ability to migrate and produce significant numbers of GABAergic neurons synthesizing the inhibitory neurotransmitter GABA. Hypoxia can lead to neuronal cell death and alterations in GABA receptor expression, and the same mechanisms were also found in epilepsy. Recent studies in our laboratory shows a substantial reduction in neuron loss and abnormal up-regulated neurogenesis induced by seizures after application of HIF-1 α inhibitor. Therefore, we hypothesize that cell therapy can supplement GABAergic neurons for rebuilding the damaged inhibitory function in hippocampus. And HIF-1α inhibitor can improve therapeutic effects in the treatment of TLE as well as avoid the malfunctioning in regenerated GABA receptors, as using HIF-1α inhibitor can abort the epileptogenic pathology process. This project aims at the mechanisms of cell therapy in restraining epileptogenesis during early-life or adult with and without the inhibition of HIF-1, studying the morphological and functional evolution of grafted NSCs or GABA progenitors labeled with MRI-optical dual-report gene. And further elaborate the specific mechanisms underlying cell therapy, provide a novel therapeutic target for epilepsy treatment.