The blood-brain barrier (BBB) is formed by tight junctions between cerebral endothelial cells expressing claudins-3, -5, and -12. Which of the following substances crosses the BBB most readily under physiological conditions?
- A CO2, O2, and ethanol — small lipid-soluble molecules that diffuse passively down concentration gradients ✓
- B Glucose — via active Na⁺-coupled secondary transport, which is the dominant mechanism because glucose is hydrophilic
- C Dopamine — because CNS dopamine deficiency in Parkinson disease is treated by systemic dopamine infusion that crosses the BBB
- D Albumin — via transcytosis through cerebral endothelial cells, maintaining brain oncotic pressure
Explanation
The BBB allows passive diffusion of small, non-polar, lipid-soluble molecules: O2, CO2, water (via AQP4 on astrocytic endfeet), and ethanol cross freely. Glucose is hydrophilic and crosses via facilitated diffusion through GLUT1 transporter (not Na+-coupled; GLUT1 is sodium-independent). This is why dopamine given systemically does not cross the BBB (it is hydrophilic and ionised at physiological pH)—instead, its precursor L-DOPA is used because it is transported across via the large neutral amino acid transporter (LAT1). Albumin and most plasma proteins are excluded from brain parenchyma; cerebral transcytosis is markedly suppressed compared to peripheral capillaries.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.