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Blood-Brain Barrier and HIV CNS Entry 

Blood-Brain Barrier and HIV CNS Entry
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date: 17 June 2019

The blood-brain barrier (BBB) actually consists of several relatively distinct barriers, operating in parallel to one another in different anatomical regions. These barriers restrict and regulate the passage of materials between the peripheral and cerebrospinal compartments. The best studied and most important of the barriers are the vascular barrier and the choroid plexus. Barrier functions arises through mechanisms associated primarily with endothelial cells (tight junctions, infrequent fenestrations, reduced pinocytosis) but also involve the capillary basement membrane, pericytes, and astrocytes. BBB function responds dynamically to the needs of the central nervous system (CNS) and for this reason the BBB is sometimes described as a "slave" of the CNS. The BBB communicates with microglia, neurons, and other cells, and it responds to a wide range of soluble factors released by these cells. Multiple transport processes, both passive and active, carry materials into and out of (efflux) the cerebrospinal fluid. Efflux mechanisms help explain why some drugs fail to reach therapeutic concentrations in the CNS; and inter-individual variations in efflux mechanisms can explain why some people are more or less sensitive to the therapeutic effects or side effects of particular CNS medications. Immune cells, once thought to be excluded from the CNS except under conditions of brain infection, are now recognized to patrol the normal CNS; and a major type of brain cell, the microglia, is derived from peripheral macrophages and may exist in some (as-yet poorly defined) equilibrium with the peripheral macrophage pool. This chapter presents these varied aspects of BBB structure and function in some detail, then builds on that fundamental understanding to discuss the BBB's role in neuroimmune interactions in both health and disease, including in HIV-1 disease.

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