DIFFUSION OF SUBSTANCES THROUGH THE BRAIN

物质通过大脑的扩散

• 批准号: 3415183
• 负责人: CHARLES NICHOLSON
• 金额: $ 23.38万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3415183
• 关键词: 6 hydroxydopamine; Cephalopoda; Chelonia; brain; cell morphology; cerebellum; cerebral ventricles; diffusion; dopamine; extracellular; image processing; laboratory rat; microelectrodes; nontherapeutic iontophoresis; optic nerve; osmotic pressure; passive transport; saltwater environment; substantia nigra

The long-term objective of this proposal is to study the real-time diffusion and fate of substances in the extracellular microenvironment of the brain. Diffusion will be measured with ion-selective micro-electrodes (ISMs), carbon fiber voltammetric microelectrodes (CFVMs), which are both working in this laboratory, and quantitative optical imaging (QOI) which will be developed. The specific aims are: 1. Characterization of basic diffusion properties in selected brain regions under different conditions. Using ISMs and QOI three investigations will made: a) Diffusion in selected neural lobes of an invertebrate, the cuttlefish, for comparison with existing vertebrate data to determine the ubiquity of diffusion parameters. b) Diffusion in the optic nerve of the rat to make a comparison between white and grey matter. c) Diffusion in the isolated turtle cerebellum bathed in media of different osmotic strength to delineate the effects of extracellular space volume on diffusion. These studies will clarify fundamental diffusion mechanisms and provide a basis for future studies of altered states in anoxic or ischemic pathologies and diffusion in the developing and ageing brain. 2. Dopamine diffusion in the striatum and the general problem of uptake. Nafion coated CFVMs and high speed cyclic voltammetry will be used to measure dopamine diffusion in slices from normal and 6-hydrooxydopamine unilaterally lesioned rat striatum. Control diffusion parameters will be measured with ISMs and QOI. Equations for Michelis-Menten uptake kinetics in complex media will be developed and applied to the analysis of dopamine migration. Diffusion and uptake of dopamine in the striatum is a key to replacement therapies for Parkinson's disease, which is simulated by the proposed lesion. Active uptake of substances commonly modifies diffusion in many parts of the brain. 3. Migration of substances at ventricular interfaces. QOI and ISMs will be used to look at substances moving across the ventricular and sub-ventricular interfaces in the isolated and perfused turtle brain. Diffusion across ventricular surfaces is a likely route for neuromodulators and is commonly employed for the administration of drugs and chemotherapy agents.

本提案的长期目标是研究实时 物质在细胞外微环境中的扩散和归宿 大脑 扩散将用离子选择性微电极测量 （ISM），碳纤维伏安微电极（CFVM），这两者都是 在这个实验室工作，定量光学成像（QOI） 将被开发。 具体目标是： 1. 脑组织基本弥散特性的表征 不同条件下的区域。 使用ISM和QOI将进行三项调查： 选择一种无脊椎动物乌贼的神经叶进行比较 用现有的脊椎动物数据来确定扩散的普遍性 参数 B）大鼠视神经中的扩散，以制备a 比较白色和灰质。C.在隔离区的扩散 海龟小脑浸泡在不同渗透强度的介质中， 描绘细胞外空间体积对扩散的影响。 这些研究将阐明基本的扩散机制，并提供一个 缺氧或缺血状态改变的未来研究基础 病理学和扩散在发展和老化的大脑。 2.多巴胺在纹状体的扩散和一般的摄取问题。 Nafion涂层CFVM和高速循环伏安法将用于 测量正常和6-羟多巴胺切片中的多巴胺扩散 单侧损伤大鼠纹状体。 控制扩散参数为 用ISM和QOI来衡量。 Michelis-Menten吸收动力学方程 在复杂介质中，将开发和应用于多巴胺的分析 迁移 多巴胺在纹状体的扩散和摄取是替代的关键 帕金森病的治疗，这是模拟提出的 损伤。 物质的主动摄取通常会改变许多细胞中的扩散。 大脑的一部分。 3. 心室界面处物质的迁移。 QOI和ISM将用于查看物质在 心室和心室下界面在隔离和灌注 龟脑 通过心室表面的扩散是神经调质 并且通常用于给药和化疗 剂.