CEREBRAL ISCHEMIA AND FREE OXYGEN RADICALS

尽管大脑对压力的反应减弱 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 也不清楚损害的机制是否与 脑缺血(脑血流量减少)和缺氧(a 血液含氧量减少)。这个项目的总体目标是 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 和低氧，并确定新生儿的表观能力 动物对脑氧供应减少的耐受与此有关 是一种自由基机制。我们假设，增加 缺血性损伤的持续时间与减少有关 脑缺血后脑血流量和氧含量的恢复 消耗，脑缺血后神经功能恢复下降 脑缺血后氧源的功能和增加 自由基，但这些变化不会那么明显 新生儿。同样，我们假设将会有一个 氧自由基释放量增加 单纯缺氧后复氧。脑缺血将由以下因素引起 静脉阻断后交叉夹闭升主动脉 洞穴。无论是新生的还是年长的动物都会出现缺血 为可变时间维护，以确定是否更改 缺血间期或给药氧衍生的游离 自由基清除剂(如超氧化物歧化酶)对 缺血后遗症。将被测量的变量 包括脑血流(放射性标记微球技术)， 脑氧耗(Fick原理)、脑功能 (诱发电位)与氧自由基的产生 (硝基蓝四氮唑法)。脑部缺氧会 通过降低激励氧含量而产生的 维持动脉血二氧化碳分压和pH值正常。在这群人中 动物的缺氧将维持在两个水平之一(5%或 10%O2)10分钟，自由基产生率 将在复氧过程中确定。根据我们的数据，我们将 能够确定氧是否来源于自由基 其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.