Fig. 1.

Interactions between various cell types in the neurovascular unit are crucial for the formation of neurovascular barriers. (A) In the CNS, vascular components, including endothelial cells (light gray), endothelial cell-derived basement membrane (endothelial BM; yellow) and mural cells [such as pericytes (pink)], together with astrocytes (purple), astrocyte-derived BM (astrocyte BM; green), neurons (gray) and microglia (orange) interact anatomically to form the neurovascular unit (NVU). The boxed area is presented in greater detail in B. (B) A schematic of the cell biological mechanisms that contribute to the neurovascular barrier properties of CNS endothelial cells. Tight junctions, formed by claudins (dark blue), occludin (maroon) and zonula occludens (light blue), limit the movement of small molecules between endothelial cells, thereby forming a paracellular barrier. Tight junction proteins interact with the cytoskeleton (F-actin, green) via zonula occludens proteins (light blue). Adherens junctions, which are formed by VE-cadherin (dark gray) as well as α-catenin (dark brown), β-catenin (medium brown) and γ-catenin (light brown), are crucial for cell-cell interactions and shear stress sensing. Endothelial cells communicate with each other via connexin-regulated gap junctions (dark green). Low rates of caveolin 1 (Cav1, pink)-dependent receptor (dashed black)-mediated transcytosis prevent trafficking of larger molecules and antibodies within CNS endothelial cells, establishing a transcellular barrier. Finally, CNS endothelial cells also contain specific active and passive transporters (purple) to facilitate the movement of nutrients between the blood and the brain/retina.