HYPOXIA OF BRAIN TISSUE SLICES

脑组织切片缺氧

• 批准号: 2263467
• 负责人: GEORGE G SOMJEN
• 金额: $ 17.57万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263467
• 关键词: acidity /alkalinity; acidosis; alkalosis; amphotericin B; calcium flux; carbon dioxide; cell morphology; cell osmotic pressure; cerebral ischemia /hypoxia; electronic stimulator; electrostimulus; high energy compound; hippocampus; interstitial; laboratory rat; membrane permeability; membrane potentials; microelectrodes; neuropharmacology; nystatin; pyramidal cells; spreading cortical depression; voltage /patch clamp

Cerebral hypoxia or ischemia leads to I. reversible failure of synaptic transmission; II. irreversible loss of neuron function, indicating cell injury; III. delayed deterioration after initial transient recovery following reoxygenation. Previous research in this laboratory has dealt with various aspects of all three phases. The present application is devoted mainly to the mechanism by which neurons lose the capacity to recover from hypoxic insult. The long-range goal of this project is a comprehensive study of the acute effects of hypoxia on central nervous tissue of mammals. Since the objective is the effect of oxygen deprivation itself separated from indirect effects and systemic changes, in vitro preparations are used. In this renewal period we will concentrate on the mechanism and causes of the transition from reversible to irreversible hypoxic change in hippocampal tissue slices. Several hypotheses derived from our previous work will be tested. Recording techniques include conventional microelectrodes, ion selective microelectrodes, and patch-clamping in whole-cell configuration. The proposed experiments will cover the following topics: l. The effects of pH on hypoxic spreading depression (SD)-like depolarization, and on recovery from the effects of hypoxia. 2. Changes of interstitial space during hypoxia, and the role of cell swelling in hypoxic SD-like depolarization. 3. Interaction of hyper-osmotic and hypo-osmotic media with hypoxia. 4. Effects of permeabilizing cell membranes to monovalent cations in hippocampal slices. 5. Membrane changes associated with loss of recovery capacity in CA1 pyramidal neurons in hippocampal tissue slices, investigated with tight seal patch-clamping in whole-cell configuration.

脑缺氧或缺血导致I.可逆性突触衰竭 传输; II.神经元功能的不可逆丧失，表明细胞 伤害; III.初始瞬态恢复后延迟劣化 再氧合后。该实验室以前的研究涉及 所有三个阶段的各个方面。本申请 主要致力于神经元失去能力的机制， 从缺氧损伤中恢复。 该项目的长期目标是对急性 缺氧对哺乳动物中枢神经组织的影响。以来 目的是缺氧本身的影响， 间接作用和全身变化，使用体外制剂。在 在这一更新时期，我们将集中研究 海马缺氧从可逆到不可逆的转变 组织切片从我们之前的工作中得出的几个假设将是 测试.记录技术包括常规的微电极、离子探针、微电极阵列和微电极阵列。 选择性微电极和全细胞结构的膜片钳。 拟议的实验将涵盖以下主题： L. pH值对低氧扩散性抑制（SD）样细胞的影响 去极化和从缺氧的影响中恢复。 2.缺氧时细胞间隙的变化及细胞因子的作用 缺氧性SD样去极化肿胀。 3.高渗和低渗介质与缺氧的相互作用。 4.细胞膜透化对一价阳离子的影响 海马切片。 5. CA 1中与恢复能力丧失相关的膜变化 海马组织切片中的锥体神经元，用tight 密封膜片钳在全细胞配置。