blood–brain barrier blood–brain barrier the blood–brain barrier (bbb) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. the blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. this system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function. blood–brain barriersolute permeability at the bbb vs. choroid plexusdetailssystemneuroimmune systemidentifiersacronym(s)bbbmeshd001812anatomical terminology the blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and large or hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of hydrophobic molecules (o2, co2, hormones) and small non-polar molecules. cells of the barrier actively transport metabolic products such as glucose across the barrier using specific transport proteins. the barrier also restricts the passage of peripheral immune factors, like signaling molecules, antibodies, and immune cells, into the cns, thus insulating the brain from damage due to peripheral immune events. specialized brain structures participating in sensory and secretory integration within brain neural circuits—the circumventricular organs and choroid plexus—have in contrast highly permeable capillaries. structure part of a network of capillaries supplying brain cells the astrocytes type 1 surrounding capillaries in the brain sketch showing constitution of blood vessels inside the brain the bbb results from the selectivity of the tight junctions between the endothelial cells of brain capillaries, restricting the passage of solutes. at the interface between blood and the brain, endothelial cells are adjoined continuously by these tight junctions, which are composed of smaller subunits of transmembrane proteins, such as occludin, claudins (such as claudin-5), junctional adhesion molecule (such as jam-a). each of these tight junction proteins is stabilized to the endothelial cell membrane by another protein complex that includes scaffolding proteins such as tight junction protein 1 (zo1) and associated proteins. the bbb is composed of endothelial cells restricting passage of substances from the blood more selectively than endothelial cells of capillaries elsewhere in the body. astrocyte cell projections called astrocytic feet (also known as "glia limitans") surround the endothelial cells of the bbb, providing biochemical support to those cells. the bbb is distinct from the quite similar blood-cerebrospinal fluid barrier, which is a function of the choroidal cells of the choroid plexus, and from the blood-retinal barrier, which can be considered a part of the whole realm of such barriers. not all vessels in the human brain exhibit bbb properties. some examples of this include the circumventricular organs, the roof of the third and fourth ventricles, capillaries in the pineal gland on the roof of the diencephalon and the pineal gland. the pineal gland secretes the hormone melatonin "directly into the systemic circulation", thus melatonin is not affected by the blood–brain barrier. development the bbb appears to be functional by the time of birth. p-glycoprotein, a transporter, exists already in the embryonal endothelium. measurement of brain uptake of various blood-borne solutes showed that newborn endothelial cells were functionally similar to those in adults, indicating that a selective bbb is operative at birth. in mice, claudin-5 loss during development is lethal and results in size-selective loosening of the bbb. function