STUDIES ON NEURONS & GLIA IN VITRO

神经元研究

• 批准号: 3396354
• 负责人: BRUCE Robert RANSOM
• 金额: $ 17.79万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396354
• 关键词: acid base balance; astrocytes; cerebral cortex; cerebral ischemia /hypoxia; developmental neurobiology; electrophysiology; extracellular; glia; histology; homeostasis; laboratory mouse; laboratory rat; membrane permeability; microelectrodes; neural information processing; neuroanatomy; neurochemistry; neurons; neurophysiology; optic nerve; tissue /cell culture; voltage /patch clamp

The proposed research represents a continuation of studies, in vitro, of some of the basic physiological and morphological properties of mammalian glia and neurons, in relation to the ionic and volume regulation of the extracellular space (ECS) of brain. The long term goals of this work are to discover how the basic properties of glia and neurons interact to account for the dynamic, but regulated, ionic and volume flucuations seen in the ECS with brain activity. A new direction for this proposal is to study this issue in a pathological circumstance; specifically, to analyze the pathophysiology of anoxia in white matter of the brain, in mature and developing animals, using the isolated rat optic nerve (RON). Isolated RONs, tissue slices from rat cortex, and cultured astrocytes, will be used in most experiments and offer several advantages over in vivo preparations, including ready access of perfusion solutions to the ECS, direct visualization of microanatomic features of the tissue cells, and great experimental flexibility. Using standard electrophysiological recording techniques, ion-sensitive microelectrodes, and the patch-clamp method, the following projects will be undertaken: 1) developmental study of glial cell physiology and morphology in the RON; 2) patch-clamp studies of single ion channels in cultured glia; 3) analysis of activity dependent and K+ - induced changes in pHo in the RON and cortex; 4) studies on the pathophysiology of anoxia in white matter, using the RON; 5) studies on the mechanism(s) of neural activity dependent and K+ - induced ECS shrinkage; 6) developmental studies on the susceptibility of white matter to anoxic injury. These studies should provide basic new information about the properties of glia and neurons, especially as these relate to ion homeostasis in brain ECS under normal and pathological conditions. These studies are broadly relevant to the clinical problems of stroke, neonatal asphyxia, and brain swelling.

拟议的研究代表了研究的延续 体外，一些基本的生理和形态学 哺乳动物神经胶质和神经元的特性，相对于离子 大脑细胞外空间（EC）的体积调节。 这项工作的长期目标是发现基本 神经胶质和神经元的特性相互作用以解释动态 但是在EC中看到的受调节，离子和体积逆转 大脑活动。 该建议的新方向是研究 在病理情况下问题；具体来说，分析 大脑白质缺氧的病理生理，成熟 并使用孤立的大鼠视神经（RON）发育动物。 孤立的Rons，大鼠皮层的组织切片和培养 星形胶质细胞将用于大多数实验，并提供几个 优于体内准备的优势，包括准备访问 ECS的灌注解决方案，直接可视化 组织细胞的微解剖特征和伟大的实验 灵活性。 使用标准电生理记录 技术，对离子敏感的微电极和斑块钳 方法，将进行以下项目：1） 神经胶质细胞生理学和形态的发展研究 罗恩2）培养的单离子通道的斑块钳研究 神经胶质； 3）分析活动依赖性和K+诱导的变化 在罗恩和皮质中的河粉中； 4）研究 使用罗恩，白质缺氧； 5）研究 神经活动依赖性和K+诱导EC的机制 收缩； 6）关于白色敏感性的发展研究 对缺氧损伤很重要。 这些研究应提供基本的新 有关神经胶质和神经元的特性的信息，尤其是 由于这些与正常的脑EC中的离子稳态有关， 病理状况。 这些研究与 中风，新生儿窒息和脑肿胀的临床问题。