ASTROGLIOSIS AND EPILEPTOGENESIS

星形胶质细胞增多症和癫痫发生

• 批准号: 2445687
• 负责人: Guy M McKhann
• 金额: $ 3.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2445687
• 关键词: astrocytes; brain electrical activity; epilepsy; extracellular; gliosis; hippocampus; histopathology; human tissue; ion transport; kainate; laboratory rat; potassium

Although glial scarring has long been associated with focal epilepsy, studies to date have failed to establish a pathophysiologic linkage. There is increasing evidence however that central nervous system astrocytes play an essential role in regulating extracellular ion homeostasis and extracellular space (ECS) size in response to neuronal activity. Preliminary results have shown that altering different glial mechanisms that regulate the extracellular environment can either result in an increase of decrease of neuronal synchronization. In normal hippocampal slices, blocking potassium uptake into glia results in epileptiform activity. In contrast, preventing ECS shrinkage antagonizes epileptiform activity in both in vitro and acute animal models of epilepsy. We propose to study astrocytic regulation of the extracellular environment in the kainate rat model of chronic temporal lobe epilepsy and in human specimens from temporal lobed epilepsy resections. We will test the hypothesis that there is altered regulation of potassium and/or ECS size by the astrocyte syncytium in gliotic hippocampus from kainate treated rats and human surgical specimens from temporal lobe epilepsy resections.

尽管神经胶质疤痕长期以来一直与局灶性癫痫有关， 迄今为止的研究未能建立病理生理学联系。 然而，越来越多的证据表明中枢神经系统 星形胶质细胞在调节细胞外离子中发挥重要作用 稳态和细胞外空间（ECS）大小对神经元的反应 活动。 初步结果表明，改变不同的胶质细胞 调节细胞外环境的机制可能会导致 神经元同步性降低的增加。 正常情况下 海马切片，阻止神经胶质细胞摄取钾会导致 癫痫样活动。 相反，防止 ECS 收缩会产生对抗 体外和急性动物模型中的癫痫样活动 癫痫。 我们建议研究细胞外星形胶质细胞的调节 红藻氨酸大鼠慢性颞叶癫痫模型的环境 以及来自颞叶癫痫切除术的人类标本。 我们将 检验钾的调节发生改变的假设和/或 红藻胶胶质海马星形胶质细胞合胞体的 ECS 大小 治疗大鼠和人类颞叶癫痫手术标本 切除术。

项目成果

Functional specialization and topographic segregation of hippocampal astrocytes.

海马星形胶质细胞的功能特化和拓扑分离。

• DOI: 10.1523/jneurosci.18-12-04425.1998
• 发表时间: 1998
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: D'Ambrosio,R;Wenzel,J;Schwartzkroin,PA;McKhann2nd,GM;Janigro,D
• 通讯作者: Janigro,D