The blood-brain barrier (BBB) restricts entry of most hydrophilic molecules into the CNS. Which of the following most accurately explains the structural basis of the BBB?
- A Tight junctions (TJ) between cerebral endothelial cells with claudin-5 and occludin, absence of fenestrae, low pinocytosis, and induction by astrocytic end-feet expressing AQP4 ✓
- B A thick basement membrane surrounding cerebral capillaries that selectively filters molecules by size and charge
- C Pericytes surrounding brain capillaries that phagocytose and destroy molecules before they reach neurons
- D Microglia forming a physical barrier at the abluminal surface of brain capillaries, preventing molecular transit
Explanation
The BBB is formed by highly specialised cerebral endothelial cells that differ fundamentally from peripheral capillary endothelium. The structural basis includes: (1) extensive tight junctions (TJ) with high expression of claudin-5, occludin, and ZO-1, abolishing the paracellular route; (2) complete absence of fenestrae; (3) very low rate of transcytosis/pinocytosis; and (4) high levels of drug-efflux transporters (P-glycoprotein, MRP). Astrocytic end-feet ensheathing >99% of the capillary surface secrete factors (including AQP4) that induce and maintain TJ expression. Pericytes (option C) regulate tone and barrier function but are not the primary barrier. The basement membrane (option B) and microglia (option D) are not the structural basis.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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