Overview

In most organs, capillaries let small solutes leak between the endothelial cells. Brain capillaries do not. The barrier is formed by the neurovascular unit:
• endothelial cells joined by continuous tight junctions (claudin-5, occludin, ZO-1), with no fenestrations and very little transcytosis;
• a continuous basement membrane;
• embedded pericytes;
• astrocyte end-feet covering almost all of the capillary surface. They induce and maintain the barrier properties and carry aquaporin-4 water channels.

What crosses depends on the substance:
• Lipid-soluble substances diffuse freely: O₂, CO₂, ethanol, nicotine, anaesthetics, and heroin (more readily than morphine).
• Water crosses through aquaporins.
• Essential polar nutrients need specific carriers: glucose (GLUT1), large neutral amino acids including L-DOPA (LAT1), monocarboxylates such as lactate and ketones (MCT1), and transferrin-bound iron (receptor-mediated transcytosis).
• Efflux pumps (P-glycoprotein, BCRP) actively expel many drugs and toxins back into the blood.
• Ionised molecules, proteins, most antibiotics and neurotransmitters such as dopamine and noradrenaline are largely excluded.
The barrier keeps the neuronal environment stable for precise signalling and protects the brain from circulating toxins, pathogens and hormonal or ionic fluctuations.

A few midline sites, the circumventricular organs, have fenestrated capillaries and no BBB, so the brain can sample the blood or release hormones into it. Sensory CVOs are the area postrema (emesis), the OVLT (osmolality, which drives ADH release) and the subfornical organ (angiotensin II, thirst). Secretory CVOs are the median eminence, the posterior pituitary and the pineal gland.

Location: Capillaries throughout the brain and spinal cord (the blood–spinal cord barrier), except at the circumventricular organs.

Parts & subdivisions

Endothelial tight junctions
Claudin-5, occludin, junctional adhesion molecules and ZO proteins seal the paracellular route.
Basement membrane and pericytes
Pericytes regulate capillary diameter and barrier gene expression; their loss leaks the barrier.
Astrocyte end-feet
Cover the capillaries; induce barrier properties; water (AQP4) and K⁺ regulation.
Transporters
GLUT1 (glucose), LAT1 (large neutral amino acids, L-DOPA), MCT1 (lactate, ketones), transferrin receptor; efflux by P-glycoprotein.
Circumventricular organs (no BBB)
Area postrema, OVLT, subfornical organ, median eminence, posterior pituitary, pineal gland.
Blood–CSF barrier
A separate barrier formed by the tight-junctioned choroid plexus epithelium and arachnoid barrier cells.

Anatomy

Development: Barrier properties develop early in fetal life under induction by neural tissue, pericytes and astrocytes. The barrier is functional but not fully mature at birth.

Function

Maintains a stable ionic and chemical environment for neuronal signalling
Protects the brain from circulating toxins, pathogens and neurotransmitters
Supplies glucose and amino acids by facilitated transport
Actively exports drugs and metabolites (efflux pumps)

Clinical significance

Drug delivery and L-DOPA

Dopamine cannot cross the BBB, but its precursor L-DOPA is carried by LAT1. Carbidopa inhibits peripheral DOPA decarboxylase but does not cross, so more L-DOPA reaches the brain with fewer peripheral side-effects such as nausea. Many drugs (e.g. most chemotherapy agents and antibiotics) penetrate poorly unless the barrier is inflamed. In meningitis, the inflamed BBB lets β-lactams in.

BBB breakdown and vasogenic oedema

Tumours (especially metastases and glioblastoma), abscesses, inflammation (MS plaques) and trauma disrupt the barrier. Plasma proteins and water leak into the extracellular space, causing vasogenic oedema, which responds to corticosteroids such as dexamethasone. Leakage of gadolinium or iodinated contrast into the tissue (enhancement) marks barrier breakdown on MRI and CT.

Kernicterus

In neonates with severe unconjugated hyperbilirubinaemia, lipid-soluble bilirubin crosses the immature BBB and stains and damages the basal nuclei, causing choreoathetosis, deafness and gaze palsy. It is prevented by phototherapy and exchange transfusion.

Compiled from standard anatomy and physiology references — see the Nervous System sources. For education only; not medical advice.