CEREBRAL ISCHEMIA AND FREE OXYGEN RADICALS

脑缺血和自由基

• 批准号: 3084028
• 负责人: JEFFREY R KIRSCH
• 金额: $ 6.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084028
• 关键词: blood flow measurement; brain disorder chemotherapy; brain metabolism; cerebral ischemia /hypoxia; chronic brain damage; enzyme substrate; evoked potentials; free radicals; hypoxia neonatorum; mature animal; neurologic manifestations; newborn animals; oxygen consumption; particle; radionuclide double label; respiratory gas analyzer; respiratory oxygenation; respiratory therapy; sectioning; spectrometry; superoxide dismutase; superoxides

Although the pathophysiologic response of the brain to a reduced oxygen availability has been studied for many years the exact mechanism by which cerebral damage is incurred is not known. It is also unclear whether the mechanism of damage is the same for ischemia (a reduction in cerebral blood flow) and hypoxia (a reduction in blood oxygen content). The overall goals of this project are to clarify the role of oxygen derived free radical mechanisms in the pathophysiology of global cerebral ischemia and hypoxia and to determine if the apparent ability of newborn animals to tolerate reduced cerebral oxygen availability is related to a free radical mechanism. We hypothesize that increasing the duration of an ischemic insult is associated with decreased recovery of post ischemic cerebral blood flow and oxygen consumption, decreased post ischemic recovery of neurologic function and increased post ischemic production of oxygen derived free radicals, but that these changes will be less marked in newborns. Likewise, we hypothesize that there will be an increased release of oxygen derived free radicals during reoxygenation after pure hypoxia. Ischemia will be induced by cross clamping the ascending aorta after occlusion of the vena cavae. In both newborn and older animals ischemia will be maintained for variable times to determine whether changing the interval of ischemia or the administration of oxygen derived free radical scavengers (e.g. superoxide dismutase) has an effect on post ischemic sequela. The variables that will be measured include cerebral blood flow (radiolabelled microsphere technique), cerebral oxygen consumption (Fick principle), cerebral function (evoked potentials) and production of oxygen derived free radicals (nitroblue-tetrazolium technique). Cerebral hypoxia will be produced by lowering the inspired oxygen content while maintaining arterial PCO2 and pH normal. In this group of animals hypoxia will be maintained at one of two levels (5% or 10% O2) for ten minutes and the rate of free radical production will be determined during reoxygenation. From our data we will be able to determine whether oxygen derived free radical mechanisms are associated with cerebral ischemia or hypoxia.

尽管大脑对减少的病理生理反应 氧气的有效性已经被研究了很多年，准确的 引起脑损伤的机制尚不清楚。 它 还不清楚损害机制是否相同 缺血（脑血流量减少）和缺氧（a 血氧含量降低）。 本次活动的总体目标 项目是阐明氧衍生自由基的作用 全脑缺血的病理生理学机制 和缺氧并确定新生儿的表观能力 动物耐受脑氧利用率降低的能力相关 到自由基机制。 我们假设增加 缺血性损伤的持续时间与减少 缺血后脑血流量和氧气的恢复 消耗，神经系统缺血后恢复下降 功能和增加缺血后产生的氧气 自由基，但这些变化在 新生儿。 同样，我们假设将会有一个 期间氧自由基的释放增加 纯缺氧后复氧。 会引起缺血 腔静脉闭塞后交叉夹紧升主动脉 卡瓦埃。 新生儿和老年动物都会出现缺血 维持可变时间以确定是否改变 缺血或使用游离氧的时间间隔 自由基清除剂（例如超氧化物歧化酶）对 缺血后遗症。 将测量的变量 包括脑血流量（放射性标记微球技术）， 脑耗氧量（菲克原理）、脑功能 （诱发电位）和氧衍生自由基的产生 （硝基蓝四唑技术）。 大脑会缺氧 通过降低吸入氧含量而产生 维持动脉 PCO2 和 pH 值正常。 在这组 动物缺氧将维持在两个水平之一（5％或 10% O2)十分钟和自由基产生率 将在复氧期间测定。 根据我们的数据，我们将 能够确定是否有氧衍生自由基 机制与脑缺血或缺氧有关。