The blood-brain barrier is an interface that seperates the brain from the blood. It impedes the influx of almost all but non-essential molecules from blood \(\to\) brain.
Structure
- Endothelium: no fenestrae, numerous tight junctions between each other, many mitochondria
- Basement membrane
- Foot processes of astrocytes: ensheath vessels, contain enzymes e.g. MAO
Barrier function
- Endothelial cell tight junctions \(\to\) minimize paracellular diffusion of hydrophilic substances
- Enzymes in astrocytes and endothelium degrade substances or alter them to be water-soluble \(\to\) cannot cross endothelium
Transport function
- Metabolic substrate, vitamins, electrolytes and antibodies are transported in controlled manner
- Passive diffusion \(\to\) must be very small and/or very lipid-soluble e.g. O2, CO2, water
- Facilitated diffusion e.g. glucose via GLUT1 channels
- Active transport e.g. of calcium
- Pinocytosis e.g. of antibodies
Areas with no blood-brain barrier
- The circumventricular organs. Either sensors that sample plasma or excretors of a hormone
- VOLT \(\to\) osmoceptor
- Pineal gland \(\to\) secretes melatonin
- Posterior pituitary \(\to\) secretes ADH
- Chemoreceptor trigger zone \(\to\) chemoreceptor that integrates vomiting signals
Drug features that facilitate movement across BBB
- Small MW, highly lipophilic
- High \(\Delta\)C \(\to\) low protein binding, low Vd, low potency (\(\therefore\)large dose), cerebral metabolism of drug)
- Substrate for active transport (e.g. lithium masquarades as sodium, valproate as lactate)