Figure 1. Schematic representation of the neurovascular unit.

A) Cellular components of the blood-brain barrier. Capillaries in the central nervous system are made up of endothelial cells (purple) which form the walls of the blood vessels, and their ablumenal surface is incompletely covered by a pericytes (green) which are embedded in the vascular extracellular matrix. Astrocytes (blue), a major glial cell population, extend cellular processes whose endfeet ensheath the blood vessels. Between the astrocytes and the vascular tube are two layers of extracellular matrix, the vascular extracellular matrix secreted by the endothelial cells and pericytes, and the glial matrix secreted by astrocytes.

B) Barrier components of the blood-brain barrier. Many of the properties of the BBB are manifested within the endothelial cells that make up the walls of the vessels. The endothelial cells are held together by tight junctions (TJs) which create tight paracellular barrier, and polarize the cells creating distinct lumenal (L) and ablumenal (AL) membrane compartments. The TJs are made up of transmembrane molecules including claudin family members, occludin and JAMs which are linked to the cytoskeleton and adherens junctions by cytoplasmic adaptors including ZO-1 and ZO-2. The endothelial cells undergo extremely low rates of transcytosis, mediated by low levels of PLVAP, limiting the transcellular movement of molecules and ions. These endothelial cells also express polarized transporters that determine the movement of many solutes across the endothelial cells. These include lumenal efflux transporters, such as Pgp and BCRP, which use ATP hydrolysis to actively transport a variety of small molecule substrates into the blood, as well as solute carriers such as Glut1, MCT1, and LAT1 which deliver specific nutrients (glucose, lactate and amino acids respectively) into the CNS. In addition endothelial cells express low levels of leukocyte adhesion molecules, including Icam1, which correlates with the low levels of CNS immune surveillance. These properties allow CNS endothelial cells to tightly regulate the movement of ions, molecules, and cells between the blood and the brain.