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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 is produced at the level of CHOROID PLEXUS ( vessels producing CSF are present, then
CSF flows within the ventricles and then enters the venous system).
Exchange between CNS and blood can be:
1) Directely: through capillaries
2) Through CSF
Two barriers:
1) 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.
2) BCSFB Endothelium is fenestrated, barrier is not made by endothelial junctions but by
choroid epithelium tight juinctions. Substances that need to pass to CSF it must cross the
rd th
choroid epithelium. Choroid plexa are present in lateral ventricle, 3 ventricle and in 4
ventricle.
3) Meningeal barrier between CSF and subarachnoid space: tight junctions in arachnoid
membrane. CSf is isolated from dura but CNS can diffuse in parenchyma but not to
overlying structures.
4) Ventricular ependyma between ventricular fluid and interstitium exchange possible.
5)
BBB and BCSFB are anatomical and functional barriers restricting the free diffusion to brain and
providinc controlled transport of nutrients and waste.
Homeostasis of brain interstitial fluid is STRICLTLY CONTROLLED.
BBB
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 (nutrients transport and removal of metabolites)
- Passive diffusion of small, lipidic molecules
- Protein carriers presence
- Limited transcytosis
- Facilited transport
The barrier presents HIGHI TRANSENDOTHELIAL RESISTANCE (TEER)
Pericytes are engulfed in basal membrane, covering capillaries and regulating proliferation,
angiogenesis and inflammatory process.
Astrocytes inducing bbb properties in endothelium source of important factors and mediators
(TGFbeta, IL-6)