DIFFUSION OF SUBSTANCES THROUGH THE BRAIN

这项建议的长期目标是研究实时 细胞外微环境中物质的扩散和去向 大脑。扩散将用离子选择微电极测量。 (ISMS)、碳纤维伏安微电极(CFVM)，它们都是 和定量光学成像(QOI)，其中 将会被开发出来。具体目标是： 1.选定大脑的基本扩散特性的特征 不同条件下的区域。 使用ISMS和QOI将进行三个调查：a)在 选择无脊椎动物墨鱼的神经叶进行比较 利用现有的脊椎动物数据来确定扩散的普遍性 参数。B)在大鼠的视神经中扩散以制造 白质和灰质之间的比较。C)在与世隔绝的 甲鱼小脑浸泡在不同渗透强度的培养液中 描述细胞外空间体积对扩散的影响。 这些研究将澄清基本的扩散机制，并提供 为未来研究缺氧或缺血状态的改变奠定基础 在发育和老化的大脑中的病理和扩散。 2.多巴胺在纹状体中的扩散和摄取的一般问题。 Nafion涂层CFVm和高速循环伏安法将用于 测量正常和6-羟基多巴胺切片中的多巴胺扩散 单侧损毁大鼠纹状体。控制扩散参数将为 用ISMS和QOI来衡量。Michelis-Menten摄取动力学方程 将在复杂介质中开发并应用于多巴胺的分析 迁移。 纹状体中多巴胺的扩散和摄取是替代的关键 帕金森氏病的治疗方法，这是由拟议的 损伤。对物质的主动摄取通常会改变许多 大脑的一部分。 3.脑室交界处物质的迁移。 QOI和ISMS将被用来观察物质在 隔离和灌流室壁及室下界面的研究 乌龟的大脑。 跨脑室表面的扩散可能是神经调节剂的一条途径 通常用于给药和化疗。 探员们。

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.