OPTICAL IMAGING OF SEIZURE PROPAGATION

癫痫传播的光学成像

• 批准号: 2260031
• 负责人: MICHAEL M. HAGLUND
• 金额: $ 7.78万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2260031
• 关键词: Primates; bicuculline; biological signal transduction; brain disorder diagnosis; brain electrical activity; brain imaging /visualization /scanning; brain mapping; brain neoplasms; disease /disorder model; electroencephalography; electrophysiology; epilepsy; glutamates; human subject; laboratory rat; language; microelectrodes; neocortex; neoplasm /cancer diagnosis; noninvasive diagnosis; photostimulus; potassium channel; sensorimotor system; temporal lobe /cortex; visual cortex

Despite many advances in our knowledge regarding the cellular and molecular mechanisms underlying epilepsy, less progress has been made in those mechanisms involved in the spread of seizure activity and surround inhibition. With a more detailed knowledge of seizure propagation and surround inhibition, pharmaceutical and surgical treatments for epilepsy could be better devised. By using optical imaging and microelectrode recordings of rat, primate, and human models of epilepsy, the P.I. has the unique opportunity to gain a better understanding of those mechanisms involved in human neocortical epilepsy. This CIDA proposal focuses on neocortical mechanisms involved in seizure propagation and surround inhibition that are common between different models of epilepsy. Three epileptogenic stimuli will be applied to in vitro rat and human neocortical slices- including low-dose or focal application of bicuculline (GABA-A antagonist); increases in the extracellular potassium concentration; or photostimulation with caged glutamate. The interaction between neocortical regions in normal conditions will be studied and the neocortical layers that are prone to the initiation of seizure activity will be characterized. Then, the preferred and regional-specific pathways used for seizure propagation will be studied with microelectrode recordings (intra-/extra-cellular) and optical imaging. The nature of "inhibitory" optical signals in areas surrounding the epileptic focus will be determined by correlating intracellular microelectrode recordings with optical imaging. Optical imaging and microelectrode recordings will also be used to examine pathways of seizure propagation and surround inhibition in the primate visual cortex and the intact human neocortex. In the primate, functional maps of visual cortex will be obtained and seizure activity will be evoked with focal applications or low-dose superfusion of bicuculline; superfusion of solutions with a high potassium concentrations; or microstimulation. In humans, as part of the routine determination of seizure thresholds for language mapping, microstimulation will be used to evoke focal epileptiform activity. In these intact preparations, the propagation of seizure activity over a larger surface area of cortex and the extent of surround inhibition will be monitored by optical imaging.

尽管我们了解了有关细胞和 癫痫的分子机制，在 那些涉及癫痫活性和包围的机制 抑制。有了更详细的了解癫痫传播和 环绕抑制作用，药物和手术治疗癫痫 可以更好地设计。通过使用光学成像和微电极 P.I.大鼠，灵长类动物和人类模型的记录有 独特的机会来更好地了解这些机制 参与人类新皮质癫痫。 该CIDA提案的重点是癫痫发作的新皮质机制 繁殖和包围抑制是不同的 癫痫的模型。将三个癫痫刺激应用于 体外大鼠和人类新皮层切片 - 包括低剂量或局灶性 施用双瓜氨酸（GABA-A拮抗剂）；增加 细胞外钾浓度；或用笼子进行光刺激 谷氨酸。新皮层区域之间的相互作用 将研究条件，并容易发生的新皮层层 将表征癫痫发作活性的开始。然后， 用于癫痫发作的首选和区域特异性途径将 用微电极记录（细胞内/细胞外）和 光学成像。区域“抑制性”光学信号的性质 围绕癫痫的重点将通过关联来确定 带有光学成像的细胞内微电极记录。光学的 成像和微电极记录也将用于检查 灵长类动物中癫痫发作繁殖和抑制的途径 视觉皮层和完整的人类新皮层。在灵长类动物中 将获得视觉皮层的地图，并将唤起癫痫发作活动 伴有焦点应用或比瓜氨酸的低剂量超级灌注； 钾浓度高的溶液的超级灌注；或者 微刺激。在人类中，作为常规确定的一部分 语言映射的癫痫发作阈值，微刺激将用于 引起局灶性癫痫样活性。在这些完整的准备工作中 在较大的皮质表面积上癫痫活性的传播和 环绕抑制的程度将通过光学成像监测。