OPTICAL IMAGING OF SEIZURE PROPAGATION

癫痫传播的光学成像

• 批准号: 2735502
• 负责人: MICHAEL M. HAGLUND
• 金额: $ 10.75万
• 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/2735502
• 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.

尽管我们在细胞和细胞方面的知识取得了许多进步 癫痫的分子机制，目前在这方面取得的进展较少 那些参与癫痫发作活动和周围扩散的机制 抑制。通过更详细地了解癫痫发作传播和 周围抑制、癫痫的药物和手术治疗 可以设计得更好。利用光学成像和微电极 大鼠、灵长类动物和人类癫痫模型的记录，P.I.有 更好地了解这些机制的独特机会 参与人类新皮质癫痫。 CIDA 的这项提案重点关注癫痫发作涉及的新皮质机制 传播和环绕抑制是不同类型之间的共同点 癫痫模型。三种致癫痫刺激将被应用到 体外大鼠和人类新皮质切片 - 包括低剂量或局部 应用荷包牡丹碱（GABA-A拮抗剂）；增加了 细胞外钾浓度；或笼式光刺激 谷氨酸。正常情况下新皮质区域之间的相互作用 将研究条件和容易发生的新皮质层 将表征癫痫发作活动的开始。然后， 用于癫痫传播的首选和区域特定途径将 通过微电极记录（细胞内/细胞外）进行研究 光学成像。区域中“抑制”光信号的性质 围绕癫痫病灶将通过关联来确定 细胞内微电极光学成像记录。光学的 成像和微电极记录也将用于检查 灵长类动物癫痫发作传播和周围抑制的途径 视觉皮层和完整的人类新皮层。在灵长类动物中，功能性 将获得视觉皮层图并诱发癫痫活动 局部应用或低剂量荷包牡丹碱灌注； 灌注高浓度钾溶液；或者 微刺激。在人类中，作为常规测定的一部分 语言映射的癫痫阈值，微刺激将用于 诱发局灶性癫痫样活动。在这些完整的准备工作中， 癫痫发作活动在更大的皮层表面积上传播， 环绕抑制的程度将通过光学成像进行监测。