This project proposes to 1) establish the relation of vascular disease to leukoaraiosis in the deep brain white matter in hypertensive and elderly humans and to correlate leukoaraiosis with the 70,000 Dalton stress protein (SP70) accumulation (a new molecular indicator of neurons and glia at risk); and 2) determine the etiology of the ubiquitous microemboli found in brains following cardiac surgery, and, with SP70, their significance. First problem: It is hypothesized that certain abnormal magnetic resonance (MR) are associated with intraparenchymal arterial/olar diseases whose ultimate effect is chronic reduction in blood transport capacity. This chronic hypoperfusion may be exacerbated by cervical carotid atherosclerosis. Why important: when these MR abnormalities, often the harbinger of more severe disease, are identified, care should be exercised in these individuals when contemplating therapy or any intervention that might decrease blood or pulse pressure. Furthermore, the conclusions reached by this research might revise downward the stage of carotid stenosis at which surgical intervention is indicated. Second problem: At least 79 % of patients will have mild, moderate or severe intellectual dysfunction following surgery assisted by cardiopulmonary bypass (CPB). Although appear to be the etiologic agent causing this brain dysfunction, little objective evidence confirming the presence of emboli is reported with the most recent techniques of cardiac surgery. Recently, microemboli have been found in autopsy brains shortly after CPB with the alkaline phosphatase (AP) method of vascular staining. The emboli range in size from 10 (mu)m to 40 (mu)m, a size that lodges in the smallest vessels of the microvasculature, and they have been found in numbers (Up to 10[6]) that might be expected to cause subtle neurological dysfunction. The outcome of surgery requiring CPB may be improved if these microemboli can be eliminated, but first their etiology must be established. Three cohorts will be studied: 1) hypertensives and elderly normotensives, and 2) postcardiac surgery patients. First project: postmortem MR will be performed on fresh autopsy brain slices. Protocol areas will be histochemically stained with the AP technique to facilitate examination of the microvasculature from the brain surface for the entire vascular length lesion to be investigated. Previous pathological correlations of deep abnormal MR signals in the brain have studied only the vessels and neuropil in the immediate abnormal area. It is believed that the proposed study will add significant predictive information to common MR imaging abnormalities. Second project: post CPB autopsy brains will have the AP microvascular stain; emboli will be identified and related to the site of appearance of a new molecular indicator of biological stress (SP70). and the identity of the embolic established.
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