Figure 2.
CNS endothelial cell properties contributing to BBB functionality: (Top) A cross-sectional view of the neurovascular unit at the level of a CNS capillary. Vessels are lined by a single-layer of non-fenestrated endothelial cells that exhibit barrier properties. Astrocytes and pericytes surround the abluminal surface of CNS endothelial cells and provide additional functional support for the establishment and maintenance of the BBB. (Bottom) A magnified view of the CNS endothelium, highlighting the four cellular properties that contribute to BBB integrity by stringently controlling the exchange of ions and nutrients between the blood and brain. (1) Specialized tight junctions prevent paracellular flux between endothelial cells. Cell-cell interactions are mediated by tight junction proteins, including junctional adhesion molecule-1 (JAM-1), occludin, and members of the claudin family. The cytoplasmic adaptor proteins ZO-1 and ZO-2 link these transmembrane proteins to the cytoskeleton. (2) Endothelial cells exhibit extremely low rates of transcytosis, as vesicular trafficking of ions and nutrients across cells is kept to a minimum. (3) Endothelial cells express influx (purple hexagons) and efflux (green hexagons) transporters that both shuttle specific nutrients into the brain and remove potentially harmful toxins and other small molecules from the brain, respectively. (4) The low expression of leukocyte adhesion molecules (LAM) aids in maintaining low levels of immune surveillance in the CNS.