CEREBRAL ISCHEMIA, VIABILITY AND OXIDATIVE METABOLISM

当脑血流量不足以维持氧化代谢时， 发生缺血性损伤，其特征在于 大脑代谢生理学的恶化， 不可逆转的伤害 尽管各种相互关联的因素 与脑损伤的进展有关， 这些尚未定义，缺血诱导的变化对 恢复不好理解，没有治疗模式已经实现 普遍接受。 拟议的研究旨在探讨 影响代谢生理学恢复（细胞功能和 代谢，以及它们之间的关系）， 哺乳动物的大脑 具体的协议集中在组织和 细胞内活动表现为细胞外 氧合、线粒体电子传递、血流、离子传递和 突触传递，因为这些变化是缺血的后果 并且可能强调这种损伤的继发性和不可逆的影响。 拟议的研究是基于“实时”，同时光学和 电极指数 大脑代谢生理学的一部分 这些将被衡量 (and有时操纵）在“稳态”和“主动”条件下 在缺血性损伤之前、期间和之后。 这种方法提供了四个 优点：1）紧密耦合的电，离子运输和代谢 脑内活动可以相互研究; 2）侵入性 可以避免生化分析的取样; 3）程度的变化， 可以说明动物中缺血诱导的变化的时间过程 4）他们提供了一个自然的历史事件，使长期的影响 可能与之前的事件有关。 目标和具体目标反映了 研究：a）线粒体、离子转运和 缺血后的电生理活性; B）促进、延迟 或禁止恢复这些功能; c）潜在的因素，或 预测，二次故障;和d）潜在的因素，或预测 对脑缺血后果的选择性脆弱性。 的 这种研究的基本前提是， 缺血的影响，以及促进或限制恢复的因素， 大脑代谢后，将导致更好的管理， 脑血管疾病

When cerebral blood flow is inadequate to sustain oxidative metabolism, an ischemic insult occurs which is characterized by a well described sequence of deteriorative changes in brain metabolic physiology which threaten irreversible damage. Although a variety of interrelated factors have been implicated in the progression to brain injury,relationships among these are not yet defined,effects of ischemia-induced changes upon recovery are not well understood and no mode of therapy has achieved general acceptance. Proposed studies are aimed toward factors that influence restoration of metabolic physiology (cell functions and metabolism,and relationships among these) following transient ischemia in mammalian brain. Specific protocols are focused upon tissue and intracellular activities manifested as extracellular oxygenation,mitochondrial electron transport,blood flow,ion transport and synaptic transmission since changes in these are consequences of ischemia and may underline secondary and irreversible effects of such insults. Proposed studies are based upon 'real-time', simultaneous optical and electrode indices of brain metabolic physiology. These will be measured (and sometimes manipulated) under 'steady-state' and 'active' conditions prior to,during and after ischemic insults. This approach offers four advantages: 1) the tightly coupled electrical,ion transport and metabolic activities in brain can be studied in terms of each other; 2) invasive sampling for biochemical assay can be avoided; 3) variations in extent and time course of ischemia-induced changes among animals can be accounted for; 4)they provide a natural history of events so that long-term effects can be correlated with prior events. Objectives and specific aims reflect research into: a) restoration of mitochondrial,ion transport and electrophysiology activity after ischemia; b) factors promoting,delaying or prohibiting recovery of these functions; c) factors underlying,or predictive of,secondary failure; and d) factors underlying, or predictive of,selective vulnerability to the consequences of cerebral ischemia. The fundamental premise of such research is that increased understanding of the effects of ischemia,and factors that promote or limit restoration of brain metabolic afterward,will lead to better management of cerebrovascular disease.