REPERFUSION AND ISCHEMIC BRAIN NECROSIS

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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.