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 多年来已经研究了氧气可用性 尚不清楚引起大脑损伤的机制。 它 还不清楚伤害机制是否相同 缺血（脑血流降低）和缺氧（A 减少血氧含量）。 总体目标 项目旨在阐明氧气得出的自由基的作用 全球脑缺血的病理生理学的机制 和缺氧，并确定新生儿的明显能力是否明显 动物耐受脑氧的可用性降低是相关的 自由基机制。 我们假设增加 缺血性侮辱的持续时间与减少有关 恢复缺血后的脑血流和氧气 消费，降低神经系统缺血后恢复 功能和增加的氧气缺血产生产生 自由基，但是这些变化在 新生儿。 同样，我们假设会有 增加氧气衍生自由基的释放增加 纯缺氧后的重氧。 缺血将被 静脉阻塞后交叉夹紧主动脉 骑士。 在新生儿和老年动物中，缺血将是 维持可变时间以确定是否更改 缺血的间隔或衍生自由的氧气给药 自由基清除剂（例如，超氧化物歧化酶）对 缺血性后遗症。 将测量的变量 包括脑血流（放射性标记的微球技术）， 脑氧的消耗（FICK原理），脑功能 （诱发电位）和衍生自由基的氧气产生 （氮蓝色四唑技术）。 脑缺氧将是 通过降低受启发的氧含量而产生 保持动脉PCO2和pH正常。 在这一组 动物缺氧将保持在两个级别之一（5％或5％ 10％O2）持续十分钟和自由基生产的速度 将在重氧过程中确定。 从我们的数据中，我们将 能够确定氧气是否衍生自由基 机制与脑缺血或缺氧有关。