THE ROLE OF NEURAL STEM CELLS IN THE DEVELOPMENT OF HUMAN EPILEPSY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项建议的目的是确定活跃的神经干细胞(NSC)增殖在长期癫痫发作后患者反复发作以及神经、认知和行为障碍的发展中所起的作用。癫痫是最常见的神经系统疾病之一。有相当数量的癫痫患者表现出癫痫发作频率逐渐增加，几乎一半的患者最终发展为癫痫，这是一种自发性反复发作的病理状态，尽管有最佳的药物治疗。癫痫患者经常经历严重的神经心理障碍，影响他们的学习、工作机会和生活质量。这一点在儿童期发作的癫痫中尤为明显。尽管进行了广泛的研究，但导致认知长期改变，有时发展为医学上难以治愈的癫痫的生物学机制仍然知之甚少。 严重顽固性癫痫最常见的发生部位是在颞叶。几项对颞叶癫痫动物模型的研究表明，在长时间惊厥发作后，NSC在3-7天内显著激活。由于到目前为止，还没有可靠的生物标志物来追踪人神经干细胞在体内的命运，这一过程还无法在癫痫患者中进行研究。最近，Savatic博士发现了NSC的代谢生物标志物，这使我们能够首次使用无创、高分辨率的质子磁共振波谱(1HMRS)来研究NSC在癫痫发作后在人脑中的命运。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to determine the role of active neural stem cell (NSC) proliferation in development of recurrent seizures and neurological, cognitive, and behavioral impairments in patients following a prolonged seizure. Seizure is one of the most common neurological disorders. A substantial number of patients who experience a seizure demonstrate progressively increased seizure frequency, and nearly half of all patients eventually develop epilepsy, a pathological condition of spontaneous recurring seizures despite optimal medical therapy. Patients with epilepsy often experience significant neuropsychological impairments, affecting their learning, job opportunities, and quality of life. This is particularly evident in childhood onset epilepsy. Despite extensive research, the biological mechanisms that lead to long-term alterations in cognition and sometimes progression to medically intractable seizures are still poorly understood. The most common site for the development of severe intractable epilepsy is located in the temporal lobe. Several studies in animal models of temporal lobe epilepsy have revealed significant activation of NSC within 3-7 days after a prolonged convulsive seizure. This process could not be studied in patients with epilepsy as, up to now, there have been no reliable biological markers to trace the fate of human NSC in vivo. Recently, a metabolic biomarker of NSC has been identified by Dr. Savatic, which enables us to investigate, for the first time, the fate of NSC in the human brain after a seizure, using noninvasive, high-resolution proton Magnetic Resonance Spectroscopy (1HMRS).