The major risk factors which are associated with an increased incidence of stroke have been known for many years. However, the basic mechanisms by which these factors lead to the increased risk are not fully understood. Preliminary studies indicate that activation of the immune system by risk factors for stroke (hypertension, hypercholesterolemia, diabetes and age) increases the risk of endothelial activation and the formation of intravascular thrombosis. By measuring the levels of cytokine and monocyte, macrophage and endothelial cell activation in the stroke-prone population and age matched controls without risk factors, an attempt will be made to characterize those factors which potentially increase the risk for activation of brain vessel endothelium as well as preparing the brain tissue (including the cerebral vasculature) for a hyperactive inflammatory response to an ischemic insult. In addition, although disease is a major cause of stroke in the U.S., no radiographic findings related to the stenosis nor specific morphologic features of the atherosclerotic plaque have been useful in predicting which will become symptomatic and which will remain asymptomatic. In this study, we are analyzing carotid endarterectomy surgical specimens from symptomatic and asymptomatic patients for leukocyte adhesion molecules on the plaque endothelial cells using immunofluorescence staining. Blood drawn at the time of preoperative testing is being examined for leukocyte and endothelial cell activation by fluorescence activated cell sorting (FACS) and baseline cytokine levels. It is hypothesized that the local release of cytokines and the expression of endothelial cell surface leukocyte receptors play a major role in the conversion of an asymptomatic plaque to a symptomatic one. Understanding the role of cytokines, leukocyte activation, and endothelial interaction in promoting the cerebral ischemic state may lead to a novel approach in future stroke prevention regimens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002888-04
Application #
2579649
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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