Which structures make up the blood-brain barrier?
- Comprises of 3 cellular layers and a basement membrane
- Together these form a barrier virtually impenetrable barrier to lipophobic molecules
Capillary Endothelium
- Interconnected by tight junctions (50-100x 'tighter' than peripheral capillaries) restricting the passage of substances from the capillaries to the brain ECF
- Differ from extracerebral capillaries in having a high density of mitochondria
- Have a relative paucity of pinocytic vesicles for vesicular transport
Basement Memebrane
- Surrounds the endothelium
- 40-50nm thick
- Rich in proteoglycans, heparin sulphate, collagen type IV and laminin
Pericytes
- Reside next to capillaries
- Possesses smooth muscle like action
Astrocytes
- A type of supportive glial cell
- Projections called foot processes ensheath >95% of vessel surface
- Secrete chemicals that reduce the permeability of the capillary endothelial cells
How does the endothelium of the blood brain barrier compare other with that at other sites?
Continuous Non-Fenestrated (General)
Continuous Non-Fenestrated (Blood-Brain Barrier)
Continuous Fenestrated
Non-continuous (Sinusoidal)
Muscle, thymus, bone, lung
Brain
Kidney
Liver
- Continuous endothelial cytoplasm without fenestrae and continuous basement membrane which restricts passage of substances across the endothelium
- Tight junctions between cells limiting paracellular movement of, ions, solutes, and water - regulation of transport varies across endothelium and influenced by both physiological and pathophysiological stimuli
- Vesicles transport substances through cytoplasm in a bidirectional pathway (transcytosis)
- Similar baseline characteristics to general non-fenestrated endothelium
- Possess very 'restrictive' tight junctions between cells to prevent paracellular transport
- Close contact with pericytes and astroctyes which aid barrier function
- Circular pores of fenestrae that penetrate the endothelium
- Thick continuous basement membrane
- Allows the passage of small macromolecules through the endothelium
- Does not form a continuous lining between the lumen and surrounding tissues
- Gaps between adjacent cells and absent basement membrane
- Poses no barrier to blood and constituents
How do substances cross the blood-brain barrier and which substances pass by each route?
Route
Examples
Free Membrane Diffusion
Small Lipophilic molecules and gases:
- O2, CO2
- Anaesthetics
- Ethanol, nicotine
Membrane Channels
Small ions and water:
- H2O
- Na, K+, Cl-
Carrier-Mediated Transport
- Energy transport systems:
- Glucose (GLUT-1)
- Lactate, pyruvate (MCT1)
- Creatine (CrT)
- Amino acid transport systems
- Large neural amino acids (LAT1)
- Neurotransmitter precursors
Receptor-Mediated Transport (via transcytosis)
- Insulin
- Leptin
- IgG
- TNFa
Adsorption mediated transport (via transcytosis)
- Histone
- Albumin
Which factors can increase the rate of transfer of substances across the blood brain barrier?
Factors that increase the rate of transfer across the blood–brain barrier include:
- High lipid solubility
- Low degree of ionisation
- Low protein binding
- Low molecular weight
- High plasma–brain concentration gradient