Blood–Brain Barrier


The blood–brain barrier consists of endothelial cells lining brain capillaries. It serves to restrict and control the movement of substances between the general circulation and brain extracellular fluid. It participates in regulating the volume and composition of fluid surrounding the brain through specific transport processes, and thus contributes to homoeostasis of the central nervous system. Some of these processes may be regulated hormonally, or modulated by adjacent cells including astrocytes. The barrier function of the blood–brain barrier is due to: (1) tight junctions that restrict movement of substances between the endothelial cells, (2) specific transport proteins that determine which substances can cross the barrier transcellularly and (3) enzymes that may degrade or alter substances prior to passage. Systemically administered drugs intended to treat neurological disorders must be designed to bypass the restrictive elements of the blood–brain barrier. Pathological conditions associated with the central nervous system may alter blood–brain barrier function.

Key Concepts:

  • The blood–brain barrier regulates brain extracellular fluid.

  • Brain capillaries form a tight barrier except in specialised areas.

  • Tight junctions restrict paracellular movement of substances across the blood–brain barrier.

  • Astrocytes contribute to differentiation of the blood–brain barrier.

  • Transport across the blood–brain barrier may be passive or active.

  • Enzymes contribute a metabolic barrier to the blood–brain barrier.

  • A strategy must be developed to deliver drugs to the brain.

  • Altered blood–brain barrier function in disease.

  • Structural and functional properties of the blood–brain barrier.

Keywords: brain extracellular fluid; cerebral capillary endothelial cells; tight junctions; multidrug resistance proteins

Figure 1.

The blood–brain barrier consists of endothelial cells lining brain capillaries. These cells are connected by tight junctions, which separate the plasmalemma into luminal (blood‐facing) and abluminal (brain‐facing) plasma membrane domains. The capillaries are surrounded by a basement membrane, and are closely associated with astrocytes, neurons and pericytes.

Figure 2.

Brain capillary endothelial cells forming the blood–brain barrier are polarised and possess distinct transport proteins in the luminal and abluminal plasma membranes. This illustration depicts a model describing some of these transporters. Organic nutrients like (AA) and glucose (G) move passively from blood‐to‐brain extracellular fluid, with the assistance of carrier systems in both plasma membranes. Sodium‐dependent amino acid (Na/AA) co‐transporters positioned at the abluminal membrane apparently serve to limit the influx of certain amino acids. Passive amino acid transporters in both membranes include systems L and y+. Conversely, sodium‐dependent amino acid transporters at the abluminal membrane include systems A, N, Bo,+, and a carrier system that mediates glutamate transport (Glu). Passive carriers for glutamine (Gln) and (Glu) are present in the luminal membrane, and in concert with sodium‐dependent transporters in the abluminal membrane apear to allow for removal of these amino acids from the brain. Regarding electrolytes, a sodium–hydrogen exchanger is thought to exist at the luminal membrane, as well as a nonspecific cationic channel (e.g. Na). A sodium–potassium ATPase (Na/K) is present at the abluminal membrane, and is thought to mediate active blood‐to‐brain movement of sodium.



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Further Reading

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Davson H, Zlokovic B, Rakic L and Segal MB (1993) An Introduction to the Blood‐Brain Barrier. Boca Raton, FL: CRC Press.

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Peterson, Darryl R(Aug 2012) Blood–Brain Barrier. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000023.pub3]