This is a renewal application for a Clinical Cerebrovascular Research Center. The mechanisms of atherosclerosis initiation and formation is being studied by light and electron microscopic examination (including scanning electron microscopy) of endothelial cell damage in areas of the aorta with increased permeability as demarcated by the uptake of Evans blue dye, in areas of restored blood flow following arterial occlusion, and following partial coronary arterial construction. The natural history of subarachnoid hemorrhage and the structural alterations of arteries of undergoing vasospasm is being studied in dogs. Measurements of intracranial and blood pressure and observations of endothelial cell damage and thrombus formation by electron microscopy are being made at the site of partial vascular constriction. The effects of high cholestrol high fat diet in the prenatal, neonatal and juvenile periods of life on cholesterol metabolism and on the development of atherosclerosis in early adulthood is being studied in miniature swine. Additional studies in the rat are being carried out on the effects of such a diet on cholesterol synthesis and degradation in the liver through enzyme assay. Studies on the effects of ischemic mechanisms on the brain are continuing with emphasis on defining the biochemical and structural changes occurring following ischemia over a period of time. Electron microscopic observations on vascular innervation have included brain capillaries, peripheral autonomic innervation of intracerebral arteries, and heart blood vessels in relation to the conducting systems.