MODULATION OF EPILEPTIFORM ACTIVITY BY GONADALSTEROIDE RATS

性腺甾醇大鼠对癫痫样活动的调节

• 批准号: 3877544
• 负责人: SYLVIA ANN VEREGGE
• 金额: --
• 依托单位: SAN JOSE STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3877544
• 关键词: anticonvulsants; disease /disorder model; epilepsy; estradiol; estrogens; gonads; laboratory rat; menstrual cycle disorder; neurons; progesterone; steroid hormone

Many epileptic women experience an increase in the frequency or severity of seizures around the time of menstruation. These seizures, often referred to as catamenial seizures, are difficult to control and, thus, pose a significant clinical problem. Much experimental evidence suggests that the variations in plasma gonadal steroid levels that normally occur during the menstrual cycle may be significant in regulating seizure frequency. Presently, however, the means by which gonadal steroids modulate epileptiform activity are not well understood. The overall goal of the experiments described in this proposal is to better understand the mechanisms by which gonadal steroids influence epileptiform activity. Using the in vitro hippocampal slice from 288 male and female Sprague-Dawley rats as a model, and the techniques of extracellular and intracellular neurophysiological recording, we will investigate the direct effects of progesterone and estradiol on an epileptogenic focus. Specifically, we will: 1) determine if progesterone or one of its metabolites suppresses epileptiform activity in the hippocampal slice, 2) determine if estradiol potentiates epileptiform activity in the hippocampal slice, 3) investigate the mechanisms by which "anticonvulsant" doses of progesterone or one of its metabolites influence neuronal activity, 4) investigate the mechanisms by which "proconvulsant" and convulsant doses of estrogens influence neuronal activity, and 5) investigate the importance of the estradiol to progesterone ratio in modulating epileptiform activity.

许多癫痫妇女的频率增加或 月经期间癫痫发作的严重程度。 这些 癫痫发作，通常被称为污染性癫痫发作，很难 控制，因此构成了重大的临床问题。 很多 实验证据表明血浆的变化 通常在月经期间发生的性腺类固醇水平 周期可能在调节癫痫发作频率方面很重要。 但是，目前是性腺类固醇的手段 调节癫痫表现活性尚不清楚。 这 本提案中描述的实验的总体目标是 更好地了解性腺类固醇的机制 影响癫痫样活动。 使用来自288名男性和女性的体外海马切片 Sprague-Dawley大鼠作为模型，以及 细胞外和细胞内神经生理记录，我们 将研究孕酮和雌二醇的直接影响 在癫痫焦点上。 具体来说，我们将：1）确定是否 孕酮或其代谢产物之一抑制癫痫样 海马切片中的活性，2）确定雌二醇是否是否 增强海马切片中的癫痫样活性，3） 研究“抗惊厥”剂量的机制 孕酮或其代谢物之一会影响神经元活性， 4）调查“突出者”和 雌激素的抽搐剂量会影响神经元活性，5） 研究雌二醇与孕酮比率的重要性 在调节癫痫样活动中。