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Colloquium C06: The Blood Brain Barrier and it's Role in Immune Priviledge in the CNS in Health and Disease

It is now apparent that endothelial cells show considerable diversity, and constitute a heterogeneous population with respect to their physiology, pharmacology and biochemistry. Specifically, endothelial cells within macrovessels (arteries and veins) differ phenotypically from those of microvessels (arterioles, capillaries and venules), and even endothelial cells from the same type of vascular segment can show functional diversity depending on organ and tissue location. Based on this awareness and the consideration that different endothelial populations might show select involvement in physiological and pathophysiological processes of the central nervous system (CNS), we have begun investigating the heterogeneity of endothelial cells along the CNS microvascular tree. We hypothesize that endothelial cells from arterioles, capillaries and venules will display differential patterns of gene expression related to the functional specifications of these microvascular tributaries. Histochemical staining of brain microvessels in situ revealed that endothelial expression of alkaline phosphatase is highly variable, showing dramatic changes particularly at branch points. Furthermore, several activities associated with blood-brain barrier function were observed to be concentrated in isolated brain capillaries in comparison to venules and arterioles. Laser capture microdissection, in combination with PCR analysis, global gene profiling, Western blotting and protein arrays, is currently being used to systematically detail the breadth of endothelial heterogeneity along the microvascular axis of the CNS. It is reasoned that understanding this complexity will allow for more selective and efficient therapeutic targeting of endothelial cells in those CNS pathologies with vascular involvement.