This is a competitive continuation proposal for a Center for the Study of Cerebrovascular Disease and Stroke. The goals are the prevention of stroke and the development of effective treatment for stroke and its consequences. Both laboratory studies and clinical studies are outlined in the request. We propose to study, by the use of appropriate animal models problems of the blood vessels supplying the brain that cannot be well studied in humans. These projects relate to: 1) the routes of fluid and solute transfer between blood vessels and perivascular space; 2) changes produced in blood vessels by hypertension and diabetes and the development of vascular disease over time as shown by scanning and electron microscopy; 3) the alteration in the endothelial cell glycocalyx that are caused by hemodynamic changes and may underlie the location of atherosclerosis or clots. The clinically related projects use the techniques of artificial intelligence in computer aided decision making, data banking and clinical study of patients with the tools of psychiatry and neuropsychology. These projects will utilize data collected from a group of stroke patients to study: 1) aphasia and the cognitive deficit underlying it, the current classification and aspects of symptom change in recovery; 2) depression poststroke including the identification of risk factors, the biological correlates, comparison with control groups, genetics, and treatment; 3) computer aided decision making in stroke including development of new artificial intelligence techniques, developing and testing multiple computer programs to assist in assessing and managing patients with stroke and develop new ways of using these systems in clinical and educational settings.