MECHANISMS OF SEIZURE CONTROL IN LIMBIC CIRCUITS

边缘系统的癫痫发作控制机制

• 批准号: 2796976
• 负责人: Janet Lynn Stringer
• 金额: $ 6.8万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2796976
• 关键词: cell death; dentate gyrus; electrophysiology; epilepsy; histochemistry /cytochemistry; interneurons; laboratory rat; limbic system; mossy fiber; neural conduction; neuroanatomy; neuropharmacology; neurophysiology; nitric oxide; nitric oxide synthase

(adapted from the applicant's abstract): The long-term goal of the research project is to understand the mechanisms of seizure onset and termination using a rat model of limbic-circuit seizures. Electrophysiological, pharmacological and histochemical techniques will be utilized. The specific aims of the present proposal are fourfold. The first hypothesis is that seizures are initiated in the brain by a combination of loss of inhibition and augmentation of excitation resulting in increased propagation of impulses through a neuronal circuit. Electrophysiological techniques will examine changes in excitation and inhibition in vivo where the circuits are intact. The second hypothesis is that the brain terminates seizure activity by the release of endogenous substances, such as nitric oxide, that act locally as antiepileptic agents. Nitric oxide synthase inhibitors will be tested for an effect on seizure onset and duration. The location and number of neurons that are NADPH-diaphorase positive will be determined after repeated seizures using histochemical techniques. The third hypothesis is that a single seizure alters the structure and function of the circuits involved in the seizure discharge, thus changing the probability of initiating a subsequent seizure in the same circuits. Changes in seizure threshold, changes in the interneuron population, sprouting of mossy fibers and cell death will be determined after a single seizure. The last hypothesis is that intrinsic properties of the dentate gyrus are sufficient to allow the expression of seizures, but inputs to the dentate gyrus regulate the onset and termination of seizures.This will be tested electrophysiologically in vitro where extrinsic and intrinsic properties of the dentate gyrus can be distinguished.

（改编自申请人的摘要）：该项目的长期目标 研究项目旨在了解癫痫发作的机制和 使用边缘回路癫痫发作的大鼠模型终止。 电生理学、药理学和组织化学技术将 被利用。 本提案有四个具体目标。 第一个假设是癫痫发作是由大脑中的 抑制丧失和兴奋增强的结合 导致脉冲通过神经元的传播增加 电路。 电生理技术将检查变化 在电路完好的情况下体内的兴奋和抑制。 这 第二个假设是大脑通过以下方式终止癫痫发作活动： 释放局部作用的内源性物质，例如一氧化氮 作为抗癫痫药。将测试一氧化氮合酶抑制剂 对癫痫发作和持续时间的影响。 地点及数量 NADPH-心肌黄酶阳性的神经元的数量将在 使用组织化学技术反复癫痫发作。 第三个假设 一次癫痫发作会改变大脑的结构和功能 参与癫痫放电的电路，从而改变概率 在同一回路中启动后续癫痫发作。 变化 癫痫阈值、中间神经元群体的变化、 苔藓纤维和细胞死亡将在单次癫痫发作后确定。 最后一个假设是齿状回的内在特性是 足以允许癫痫发作的表达，但输入 齿状回调节癫痫发作的发作和终止。这将 在体外进行电生理学测试，其中外在和内在 可以区分齿状回的特性。