Figure 1

A generic brain barrier. Adult mammalian brain barriers reduce uncontrolled leakage by constituting a monolayer of cells characterized by intercellular tight junctions, decreased macropinocytosis, and decreased fenetrae. Variations on this theme are seen at the vascular brain barrier, blood-CSF barrier, and the specialty CNS barriers such as the blood-retinal barrier. Most brain barriers have a combination of the other features shown. Pores are saturable transporters that can be energy dependent (as exemplified by P-glycoprotein) or energy independent (GLUT-1), located at the luminal or abluminal membrane, and transport bidirectionally or unidirectionally into or out of the cytoplasm. Saturable transport can also be vesicular based and brain barriers likely have many types of vesicular systems (for example, receptor-mediated transcytosis, clathrin-dependent transport, podocytosis, and caveolae). Scaffolding (for example, actin) is likely highly dynamic and involved in tight junction function and vesicular trafficking. Barrier cells contain receptors (binding sites coupled to intracellular machinery) as well as transporters (binding sites coupled to machinery involved in translocation of the ligand). Brain barriers are enzymatically active and this activity can act as another layer of barrier, and they can secrete substances such as cytokines, nitric oxide, and prostaglandins from either their CNS or peripheral side.