CHARACTERIZATION AND DEVELOPMENT OF A SEIZURE FOCUS

药物难治性颞叶癫痫（TLE）通常是治疗 通过手术切除颞叶的前端， 整个海马体。 这个组织提供了一个独特的机会 用于检查人类癫痫病灶的特征。 这些信息也可以证明对外科医生有用， 开发新的策略来激活癫痫发作的焦点。 这 这项提案旨在检查人类致癫痫组织， 假设其增加的兴奋性可以在 其神经递质系统的重组和/或 介导神经递质作用的过程。 对这个和 谷氨酸神经递质受体系统的分布 (GLU)、GABA、生长抑素（SOM）、神经肽Y（NPY）和强啡肽 (DYN)将用放射自显影方法进行研究。 第2 信使腺苷酸环化酶和磷酸肌醇系统将是 用（3 H）PDBu定位以标记蛋白激酶C，用（3 H）IP 3定位以标记 IP 3受体和（3 H）-forskolin标记Gs腺苷酸 环化酶复合物 为了评估的生物合成的 肽SOM，NPY和DYN，原位杂交实验将 就这么定了 此外，原癌基因蛋白的分布 将用免疫细胞化学方法检测c-fos，以确定其是否 与人类癫痫发作有关 Giant 2D凝胶 致痫组织的电泳将试图确定 任何蛋白质单位的癫痫病灶。 热诱导大鼠 癫痫发作将被评价为人类TLE的非肿瘤模型 起源，并用于研究热性惊厥和发育 这种扣押的结果。 2-脱氧葡萄糖代谢图 活性和表达将被用来确定起源 以及癫痫的传播 神经元计数;轻度和 电镜免疫细胞化学定位神经活性 物质（GABA、谷氨酸、SOM、NPY、DYN）;放射自显影 这些物质的受体的映射;和第二信使 系统;沿着肽的原位杂交实验 生物合成将决定诱导的变化的相似性 老鼠的癫痫发作与人类的癫痫发作相比。 的后果 在成年大鼠海马诱发癫痫发作 将对组织进行评估，以确定是否存在敏感的 在此期间，热性惊厥导致成人发作癫痫发作。

Medically intractable temporal lobe epilepsy (TLE) is often treated by surgical removal of the anterior tip of the temporal lobe and the entire hippocampus. This tissue affords an unique opportunity for examining the characteristics of a human epileptogenic focus. Such information could also proove useful to the surgeon for development new strategies for in activating a seizure focus. This proposal aims at examining human epileptogenic tissue and testing the hypothesis that its increased excitability could be found in the reorganization of its neurotransmitter systems and/or the processes that mediate neurotransmitter action. To this and the distribution of nertotransmitter receptor systems for glutamate (GLU), GABA, somatostatin (SOM), neuropeptide Y (NPY) and dynorphin (DYN) will be studied with autoradiographic methods. The 2nd messenger adenylate cyclase and phosphoinositide systems will be localized with (3H)PDBu to label protein kinase C, (3H)IP3 to tag the IP3 receptor, and (3H)-forskolin to label the Gs adenylate cyclase complex. In order to assess the biosynthesis of the peptides SOM, NPY and DYN, in situ hybridization experiments will be done. Further, the distribution of the protooncogene protein c-fos will be examined immunocytochemically to determine if it is involved in human seizures as in animals. Giant 2D gel electrophoresis of epileptogenic tissue will attempt to identify any proteins unit to the seizure focus. Rats with heat induced seizures will be evaluated is a model for human TLE of non-tumor origin, and for the study of febrile seizures and the developmental outcome of such seizures. 2-deoxyglucose mapping of metabolic activity and for expression will be used to determine the origin and spread of seizures in these rats. Neuronal counts; light and electron microscopic immunocytochemical localization of neuroactive substances (GABA, Glutamate, SOM, NPY, DYN); autoradiographic mapping of the receptors for these substances; and second messenger systems; along with in situ hybridization experiments for peptide biosynthesis will determine the similarity of the changes induced by seizures in the rat to those of the human. The consequences of seizures induced in neonatel rats on their adult hippocampal organization will be evaluated to determine if there are sensitive periods during which febrile seizures lead to adult onset seizures.