What are the functions of the blood–brain barrier?

The blood–brain barrier (BBB) is a physiological, cellular and metabolic barrier at the level of the cerebral capillaries. Their permeability properties restrict the free movement of substances between the capillaries and the extracellular fluid (ECF) of the brain. The BBB has several functions:

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  To maintain a constant extracellular environment within the central nervous system (CNS). This is arguably the most important feature. The concentration of solutes in blood varies considerably, and neuronal function may be adversely affected if neurons are directly exposed to this variation. For example, exercise produces changes in plasma pH and K⁺ concentration that may depress neuronal activity if transmitted to the CNS.

  
  
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  To protect the brain from harmful or neuroactive blood-borne substances.

  
  
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  To prevent the release of CNS neurotransmitters into the systemic circulation.

What are the anatomical layers of the BBB?

The BBB comprises three layers:

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  Capillary endothelial cells, interconnected by tight junctions, restricting the passage of substances from the capillaries to the brain ECF. The capillaries of the BBB differ from extracerebral capillaries in having a high density of mitochondria.

  
  
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  A thick basement membrane, which lies beneath the endothelial cells.

  
  
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  Astrocyte foot processes. Astrocytes are a type of supportive glial cell with projections called foot processes that encircle and are closely applied to the capillaries. Astrocytes secrete chemicals that reduce the permeability of the capillary endothelial cells. In contrast, the choroid plexus is not surrounded by astrocytes, and its endothelial cells are therefore highly permeable.

These three layers form a virtually impenetrable barrier to lipophobic molecules, comparable to a continuous capillary.

How do substances cross the BBB?

Some signalling and nutritional substances gain entry to the brain ECF through a number of mechanisms:

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  Simple diffusion. Small, lipid-soluble molecules can cross the phospholipid bilayers of the BBB by simple diffusion, in common with cellular barriers elsewhere in the body. Examples include O₂, CO₂, ethanol and steroid hormones.

  
  
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  Active transport. The passage of small ions across the BBB, such as Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl‾, HCO₃‾ and H⁺, is controlled by the membrane, including transport processes. This means that blood and CSF may differ in pH and ion concentrations. The high density of mitochondria in the cerebral capillaries reflects the high metabolic activity of this process.

  
  
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  Facilitated diffusion. Some small molecules are transported across the BBB by facilitated diffusion along their concentration gradients:

  
  
  
  
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     – Glucose is transported by GLUT1 transporters, whose transport function does not require ATP.

     
     
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     – Water is transported through pores called aquaporins.

  
  
  
  
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  Pinocytosis. Other molecules (e.g. insulin) are thought to cross the BBB by pinocytosis (see Chapter 4).