AGE RELATED SEIZURE SUPPRESSION

年龄相关的癫痫发作抑制

• 批准号: 3400539
• 负责人: SOLOMON L. MOSHE
• 金额: $ 21.06万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3400539
• 关键词: GABA receptor; aging; animal age group; autoradiography; convulsants; deoxyglucose; developmental neurobiology; dosage; epilepsy; generalized seizures; histochemistry /cytochemistry; immature animal; in situ hybridization; infant animal; laboratory rat; muscimol; neuropharmacology; protein isoforms; substantia nigra

The objective of this proposal is to identify mechanisms involved in the suppression of seizures as a function of age. Ongoing studies suggest that the increased seizure susceptibility of the immature brain may be due to age-specific differences in the GABAA receptor subtypes within the substantia nigra (SN), a site that is crucial for the control of seizures in adults. The aims are to determine 1) whether there are differences in nigral GABAA receptor isoforms as a function of age; 2) whether there is a different functional role of nigral GABAA receptor isoforms on seizures as a function of age and drug dosage; 3) the nigral GABAA sensitive output systems involved in the modification of seizures as a function of age, drug and dose. Methods include in vitro studies (in situ hybridization histochemistry) to determine the ontogeny of particular GABAA isoforms; in vivo studies to determine the seizure susceptibility of rats of various ages after intracranial microinfusions of relatively specific GABAA agents in the SN via chronic indwelling cannulae in the flurothyl model of epilepsy; and deoxyglucose autoradiographic studies to map the nigral efferents activated by the relatively specific GABAA agents. Rats of various ages throughout development will be used to determine the maturational profile of the SN-mediated seizure modification. The goal is to develop a better understanding of the mechanisms that participate in the suppression of seizures with maturation. These studies may lead to the development of new therapeutic treatments that will compensate for the maturational state of the CNS.

该提议的目的是确定涉及的机制 抑制癫痫发作是年龄的函数。 正在进行的研究表明 未成熟大脑的癫痫发作敏感性提高可能是由于 GABAA受体亚型的年龄特异性差异 黑质尼格拉（SN），一个对控制癫痫发作至关重要的地点 在成年人中。 目的是确定1） nigral Gabaa受体同工型随着年龄的增长； 2）是否有 nigral Gabaa受体同工型在癫痫发作中的不同功能作用 年龄和药物剂量的功能； 3）nigral gabaa敏感输出 与年龄，药物变化有关的系统涉及癫痫发作的系统 和剂量。 方法包括体外研究（原位杂交 组织化学）确定特定GABAA同工型的个体发育；在 体内研究以确定各种大鼠的癫痫发作敏感性 相对特异性GABAA药物的颅内微型诱导后的年龄 在SN中通过慢性留置插管 癫痫;和脱氧葡萄糖放射自显影研究以绘制nigral 相对特异的GABAA药物激活的侵蚀。 老鼠 整个开发过程中的各种年龄将用于确定 SN介导的癫痫修饰的成熟度。 目标是 为了更好地理解参与的机制 抑制癫痫发作。 这些研究可能导致 开发新的治疗疗法，以补偿 中枢神经系统的成熟状态。