CEREBRAL ISCHEMIA AND FREE OXYGEN RADICALS

虽然大脑对降低的脑电的病理生理反应 多年来，人们一直在研究氧气的可用性， 引起脑损伤的机制尚不清楚。 它 也不清楚损伤的机制是否与 缺血（脑血流量减少）和缺氧（ 血氧含量降低）。 本项目的总体目标 项目是澄清氧衍生自由基的作用， 全脑缺血的病理生理机制 和缺氧，并确定新生儿的明显能力， 动物耐受脑氧供应量减少与 一种自由基机制。 我们假设， 缺血性损伤的持续时间与降低的 缺血后脑血流量和氧的恢复 消耗，缺血后神经功能恢复减少 功能和增加缺血后氧的产生 自由基，但这些变化将不太明显， 新生儿 同样，我们假设会有一个 增加释放氧衍生的自由基， 单纯缺氧后复氧。 缺血将由 阻断静脉后交叉夹闭升主动脉 洞穴 在新生儿和老年动物中， 保持可变的时间，以确定是否改变 缺血间隔或给予氧衍生的游离 自由基清除剂（如超氧化物歧化酶）对 缺血后后遗症 将被测量的变量 包括脑血流（放射性标记微球技术）， 脑耗氧量（Fick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）。 大脑缺氧会 通过降低吸入的氧气含量而产生， 维持动脉二氧化碳分压和pH值正常。 在这群 动物缺氧将维持在两个水平之一（5%或 10%O2）10分钟和自由基产生速率 将在复氧期间确定。 根据我们的数据， 能够确定是否氧衍生自由基 机制与脑缺血或缺氧有关。

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.