Anatomia dell'uomo - Blood brain barrier

Blood brain barrier

Early experiments

Injection of a colorant in systemic circulation of a rat  diffusion in every system but the CNS. Injection of the colorant in CNS, it remains confined within the CNS (in brain and CSF)  other tissues are not coloured. A barrier between the CNS and systemic circulation must be present but a communication should be present between CSF and brain: a blood brain barrier (BBB) and a blood – CSF barrier (BCSFB) are present.

CSF production and flow

CSF is produced at the level of the choroid plexus (vessels producing CSF are present, then CSF flows within the ventricles and then enters the venous system).

Exchange between CNS and blood

• Directly: through capillaries
• Through CSF

Two barriers

• BBB  between plasma and interstitial fluid. Defined by the histologic characteristics of brain and vessels (pericytes, basement membrane, astrocytes processes): endothelial cells own tight junctions (no pores nor fenestrations). In intraparenchymal vessels and pial vessels.
• BCSFB  Endothelium is fenestrated, barrier is not made by endothelial junctions but by choroid epithelium tight junctions. Substances that need to pass to CSF must cross the choroid epithelium. Choroid plexa are present in the lateral ventricle, 3rd ventricle, and in the 4th ventricle.
• Meningeal barrier  between CSF and subarachnoid space: tight junctions in the arachnoid membrane. CSF is isolated from dura but CNS can diffuse in parenchyma but not to overlying structures.
• Ventricular ependyma  between ventricular fluid and interstitium  exchange possible.

BBB and BCSFB are anatomical and functional barriers restricting the free diffusion to the brain and providing controlled transport of nutrients and waste. Homeostasis of brain interstitial fluid is strictly controlled.

BBB functions

The BBB acts as an active interface between circulation and CNS  dual functions, barrier and carrier (isolation and nutrient transport).

Barrier functions

• Restriction of free movement of water-soluble compounds between adjacent cells given by intraendothelial tight junctions.
• Enzymatic barrier  enzymes able to degrade different compounds.
• Transporters are present  efflux.
• Low level of endocytosis and transcytosis.

Carrier functions

• Passive diffusion of small, lipidic molecules.
• Protein carriers presence.
• Limited transcytosis.
• Facilitated transport.

The barrier presents high transendothelial resistance (TEER).

Role of pericytes and astrocytes

Pericytes are engulfed in the basal membrane, covering capillaries and regulating proliferation, angiogenesis, and inflammatory process. Astrocytes  inducing BBB properties in the endothelium, source of important factors.