CLINICAL RESEARCH PROGRAM FOR THE PARTIAL EPILEPSIES

部分性癫痫临床研究计划

• 批准号: 3099230
• 负责人: JEROME NONE ENGEL
• 金额: $ 97.78万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3099230
• 关键词: electroencephalography; human subject; partial seizure; psychobiology; temporal lobe /cortex disorder

The Clinical Neurophysiology Program (CNP) at UCLA makes use of the unique opportunities provided by an epilepsy surgery facility to carry out direct research on the human brain. In past years, emphasis was placed on clinical research directed toward improving the diagnosis and surgical treatment of epilepsy, although basic research has always been an important part of the program. More recently, resective surgery has become sufficiently accepted as a safe and effective mode of treatment for partial epilepsy to allow clinical activities of the CNP to be supported by hospital funds or supplemented by grants awarded to develop specific diagnostic techniques. Since the beginning of our last renewal, we have requested support only for basic research projects that take advantage of knowledge gained from animal studies and the clinical setting to investigate fundamental mechanisms of normal and abnormal human brain function. Information from patients in our epilepsy surgery facility will be utilized by a multi-disciplinary team of basic and clinical neuroscientists to define anatomical, physiological and metabolic substrates of normal and epileptiform cerebral processes, and to determine how epilepsy-related pathological processes might interfere with normal neuronal integration to disrupt behavior during, and between, seizures. Specifically, we propose to: 1.) examine alterations in cellular morphology and neurotransmitter function in epileptogenic tissue, 2) relate these findings to results of in vivo physiological studies of neuronal activity at the unit level and of spontaneous and stimulation-induced field potentials; 3.) identify aberrant axons and synapses in epileptogenic tissue which may account for hyperexcitability and seizure generation using selective staining, electron microscopy, and in vitro physiological techniques for recording from hippocampal slices; 4.) examine anatomical and physiological substrates of memory and control of cardiorespiratory functions; and 5.) carry out interactive and correlative studies with positron emission tomography to determine if metabolic patterns induced by electrical stimulation of the brain can be used to trace normal and epileptogenic cerebral pathways, and to characterize the functional significance of interictal hypometabolism. The long-term objectives of the CNP are: 1) To reveal cellular and synaptic mechanisms of epileptogenesis in order to suggest new medical, as well as surgical, approaches to antiepileptic therapy; 2.) to better understand the neuronal basis of normal human behavior and mechanisms of pathological disruption that result in abnormal behavior, in order to prevent or more effectively treat behavioral disturbances associated with epilepsy and other neurological disorders; and 3.) to establish the most effective and efficient presurgical evaluation protocol for epileptic patients who are candidates for resective surgery, in order to allow the greatest number of patients to benefit from this procedure.

加州大学洛杉矶分校的临床神经生理学课程(CNP)利用独特的 由癫痫外科机构提供的机会直接进行 对人脑的研究。在过去的几年里，重点放在 旨在提高诊断和外科治疗水平的临床研究 治疗癫痫，尽管基础研究一直是一个重要的 这是计划的一部分。最近，切除手术已经成为 被充分接受为一种安全有效的治疗方式 癫痫使CNP的临床活动得到支持 医院资金或辅以赠款，以开发特定的 诊断技术。自从我们上次更新以来，我们已经 仅为利用以下优势的基础研究项目请求支持 从动物研究和临床环境中获得的知识 探讨人脑正常和异常的基本机制 功能。我们癫痫手术中心患者的信息将 可由基础和临床的多学科团队使用 神经学家定义解剖学、生理学和新陈代谢 正常和癫痫样脑突起的底物，并确定 癫痫相关的病理过程如何可能干扰正常 神经元整合，以破坏癫痫发作期间和发作之间的行为。 具体而言，我们建议：1.检查细胞的变化 致痫组织的形态与神经递质功能，2)相关 这些发现与活体神经元生理学研究的结果相一致 单位水平上的活动以及自发和刺激诱导的场 潜力；3.)致痫过程中异常轴突和突触的识别 可能导致过度兴奋和癫痫发作的组织 选择性染色、电子显微镜和体外生理学 从海马区脑片记录的技术；解剖检查 和心肺功能记忆和控制的生理基础 功能；和5.)开展互动和相关研究 用正电子发射断层扫描确定辐射诱导的代谢模式 对大脑的电刺激可以用来追踪正常和 致痫的脑通路，并表征功能性 发作间期低代谢的意义。该计划的长远目标 CNP是：1)揭示癫痫发生的细胞和突触机制 为了建议新的内科和外科治疗方法 抗癫痫治疗；2.)为了更好地了解神经细胞的基础 正常的人类行为和由此导致的病理破坏机制 在异常行为中，为了预防或更有效地治疗 与癫痫和其他神经性疾病相关的行为障碍 障碍；以及3.)建立最有效、最高效的 候选癫痫患者的术前评估方案 对于切除手术，为了让最大数量的患者 从这一过程中受益。