REPERFUSION AND ISCHEMIC BRAIN NECROSIS

描述(调查人员摘要)：将检验假设 在缺血后，再灌流的数量水平会影响 导致神经元坏死。建立了一种计算机控制的大鼠模型 在这种情况下，有可能保持恒定的大脑灌注量 压力，局部脑组织PO2百分比，或任何其他持续 血流量监测指标。控制这些指标是可能的 在缺血期间以及在再灌流期间。他们的数量 与血流的关系将通过间歇性测量 当地脑血流量被H3清除。在初步实验中，我们有 证明这种程度的控制在以下时期是可行的 缺血和再灌流1小时以上。一种持续不断的侮辱 会造成严重的组织损伤，之后会有一段时间 不同实验中不同水平的再灌流，包括10 %、25%、50%、100%和150% 缺血前水平。在这些不同的水平上控制再灌注将 使因再灌流而加重的水肿从 前述缺血的严重程度，使之能够独立评估 缺血和再灌流对神经元坏死和水肿的作用。 在灌流固定后，将通过计数 甲苯胺蓝染色切片中死亡神经元的500微米 电极，使损伤与病灶具有高度特异性的相关性 血流量和PO2百分比的变化。在相同的切片中，细胞周围 清除间隙和神经束空泡化也将被评估为 组织浮肿。在平行实验中，新鲜组织比重将 用溴苯/煤油柱浮选法测定 对小于1 mm立方体的小体积的许可评估也很高 与电极位置相关。的独立贡献 再灌流水平的神经元损伤和去水肿因此将是可能的 定量评估。

DESCRIPTION (Investigator's Abstract): The hypothesis will be examined that following ischemia, the quantitative level of reperfusion affects the resulting neuronal necrosis. A computer-controlled rat model was developed in which it is possible to maintain a constant level of cerebral perfusion pressure, local brain tissue PO2 percent, or any other continuously monitored index of blood flow. It is possible to control these indices during ischemia as well as during reperfusion. Their quantitative relationship to blood flow will be documented by intermittent measurment of local CBF by H3 clearance. In preliminary experiments, we have demonstrated that this degree of control is feasible for periods of ischemia and of reperfusion of more than an hour. A constant insult which produces significant tissue damage will be followed by a period of constant reperfusion at different levels in different experiments, including 10 percent, 25 percent, 50 percent, 100 percent and 150 percent of the preischemic level. Control of reperfusion at these different levels will serve to uncouple the aggravation of edema due to reperfusion from the severity of the foregoing ischemia, enabling evaluation of the independent contributions of ischemia and reperfusion to neuronal necrosis and edema. Neuronal injury will be assessed after perfusion-fixation by counting of dead neurons in toluidine blue stained sections taken with 500 microns of the electrode, permitting highly specific correlation of injury with focal blood flow and PO2 percent changes. In the same sections, pericellular clear spaces and neuropil vacuolation will also be assessed as one index of tissue edema. In parallel experiments, fresh tissue specific gravity will be measured by the bromo-benzene/kerosene column flotation methdod, to permit assessment of small volumes less than 1 mm cubed also highly correlated with electrode location. The independent contributions of reperfusion level of neuronal injury and to edema will thus be possible to assess quantitatively.