The primary objective of the proposed work is to continue to investigate the following hypothesis: Hypertension and advanced age, the two major risk factors for stroke create a state in which the probability of an interaction between monocyte/macrophages and endothelial cells which could lead to local thrombosis or hemorrhage in focal regions of the brain vasculature is increased. Our preliminary data have demonstrated that animals with stroke-risk factors, when provoked by an appropriate stimulus, release more tumor necrosis factor (TNF-a) and undergo a more intense activation of hemostatic and proinflammatory mechanisms than risk factor-free controls probably as a result of a more vigorous interaction between their monocyte/macrophages and endothelium. The general plan for the next three years is to compare the activity and functional state of stimulated monocyte/macrophages and endothelium from animals with and without risk factors for stroke. The analyses will explore the possibility that several risk factors for stroke are initially associated with a change in endothelium.
