Blood–Brain Barrier

Abstract

The blood–brain barrier consists of specialised endothelial cells primarily 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 within and surrounding the central nervous system through specific transport processes and thus contributes to its homoeostasis. Some of these processes may be regulated hormonally or modulated by adjacent cells including astrocytes and pericytes. The barrier function of the blood–brain barrier is due to (1) tight junctions that restrict the 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 and pericytes contribute to differentiation and function 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.
  • Delivery of drugs to the brain requires a strategy to by‐pass the blood–brain barrier.
  • Blood–brain barrier function may be altered in the context of neurological disorders.

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

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 amino acids (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) cotransporters 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 glutamate (Glu) are present in the luminal membrane, and in concert with sodium‐dependent transporters in the abluminal membrane appear to allow for removal of these amino acids from the brain. Regarding electrolytes, a sodium–hydrogen exchanger is present in the luminal membrane, as well as an apparent 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

Haddad‐Tovolli R, Dragano NRV, Ramalho AFS, et al. (2017) Development and function of the blood‐brain barrier in the context of metabolic control. Frontiers in Neuroscience 11: 224–246.

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Peterson, Darryl R(Nov 2019) Blood–Brain Barrier. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000023.pub4]