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Volume 5, Supplement 1, 2008

Volume 5, Supplement 1, 2008

Table of Contents

Injuries to the Vascular Endothelium: Vascular Wall and Endothelial Dysfunction Virchow’s Triad 2008
Vascular endothelial injury has multiple elements, and this article focuses on ischemiarelated processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte–endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation. [Rev Neurol Dis. 2008;5(suppl 1):S4-S11]
Virchow’s Triad: The Vascular Basis of Cerebral Injury Virchow’s Triad 2008
Both the large arteries and microvascular beds of the central nervous system respond to injury by initiating processes compatible with Virchow’s triad: alterations in the microvascular permeability barrier, reduction in flow with the target bed, and/or thrombosis of brain-supplying arteries and of the microvasculature. This is particularly true during focal cerebral ischemia. The temporal and topographical coincidence of neuron injury and microvessel response during focal ischemia has suggested that neuron-microvessel interactions could be bidirectional. The neurovascular unit offers a conceptual and structural framework with which to examine events within the microvasculature and their impact on neuron integrity, with the participation of the intervening astrocytes, matrix, and other supportive cells (eg, pericytes and oligodendroglia). Activation of the endothelium and of coagulation, capture of leukocytes, and increased microvessel permeability lead to the focal “no-reflow” phenomenon. Decreased shear stress is a component of the evolving ischemia. Strategies that inhibit the interactions within the microvasculature have been shown to prevent no-reflow and improve neurological outcome. It is, therefore, possible that addressing the processes of Virchow’s triad in the setting of focal ischemia could promote neurovascular function. [Rev Neurol Dis. 2008;5(suppl 1):S12-S21]
Blood Constitution: Platelet Aggregation, Bleeding, and Involvement of Leukocytes Virchow’s Triad 2008
Normally functioning endothelial cells prevent exposure of the circulating blood to thrombogenic components of the subendothelial matrix. When the vascular endothelium is injured or denuded, blood cell components are attracted to the vessel wall, where they aggregate. Endothelial damage anywhere in the body can induce hypercoagulability and contribute to the onset of brain and myocardial infarction. The components of Virchow’s Triad—blood flow conditions, blood components, and vascular walls—all contribute to the formation of pathological thrombi. Improving any one component results in reduction in the rate of thrombotic disease by directly and indirectly improving the function of other contributors. Evidence supports the effectiveness of antiplatelet and anticoagulant therapy in the prevention of brain and myocardial infarction. [Rev Neurol Dis. 2008;5(suppl 1):S22-S27]
Summation Virchow’s Triad 2008