The blood-brain barrier (BBB) prevents passage of certain substances into the CNS. Which of the following statements about BBB transport is MOST accurate?

• A Lipophilic molecules require specific carrier proteins to cross the BBB while hydrophilic molecules cross freely by diffusion
• B Glucose crosses the BBB via facilitated diffusion through GLUT1 transporters on both luminal and abluminal membranes of brain endothelial cells ✓
• C Amino acids are excluded from the brain by the BBB regardless of lipophilicity
• D The BBB is absent around the hypothalamus allowing unrestricted substance entry

Explanation

Glucose crosses the blood-brain barrier via facilitated diffusion through GLUT1 (SLC2A1) transporters, which are expressed on both the luminal (blood-facing) and abluminal (brain-facing) membranes of brain capillary endothelial cells. GLUT1 allows bidirectional glucose transport down its concentration gradient, without energy requirement. GLUT3 on neurons then takes up glucose from interstitial fluid. Lipophilic molecules cross the BBB more readily by passive diffusion; the BBB restricts hydrophilic molecules, not lipophilic ones. Amino acids cross via specific carrier systems (LAT1 for large neutral AAs, CAT for cationic AAs). The circumventricular organs (area postrema, organum vasculosum, subfornical organ, etc.) lack a BBB—not the entire hypothalamus; only specific nuclei are outside the BBB.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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