L4 Blood Brain Barrier Flashcards
What did Edwin Goldmann do?
Proved there was a barrier between the blood and the CSF/brain
WHy do we need a BBB?
- Central Nervous System needs to maintain an extremely stable internal fluid environment which is an absolute requirement for reliable synaptic communication between nerve cells.
- The Blood-Brain Barrier is also a protective barrier which shields the central nervous system from circulating neurotoxic substances in blood which are produced by metabolism or are ingested in the diet or otherwise acquired from the environment
Properties of the BBB
Effectively the same as Endothelial cell membranes
- can dictate what goes in and out
No free diffusion pathway
GLIAL CELLS - regulating cells
- exchange nutrients
- don’t generate AP’s
- have tight junctions
Pericyte
- produces the inital barrier
- then maintained by Glial cells
Organization of the Cerebral Endothelial Tight junction
Several important proteins crucial to the BBB
- Claudin 3 & 5
- very imp, knocking these out in mice causes a leaky csf and kills the mice
- Other imp proteins include:
- occludin
- cadherin
- JAM - junction associated molecule
Choroid Plexus
Important barrier region
In the lateral and 4th ventricles of the brain
Has tight junctions between the ependymal epithelium (outer layer)
Capillary has fenestrations
Difference between BBB and Choroid plexus
Tight Junctions:
- BBB - in the ENDOTHELIUM
- Choroid plexus - in the EPITHELIUM
Circumventricular Organs
places in the brain which are leaky and allows fluid content from body to enter so it can be sampled
- No tight junctions - easy diffusion through here
- Changes in blood solutes can cause changes in behaviour, activity of the CNS
- Selectively very permeable areas in th brain
CVO Sensory: monitor what’s going on in the blood
Neurohaemal Secretory: Release things into the blood
Routes across the BBB
-
Passive (Simple) Diffusion
- Small lipid soluble molecules. Blood gases.
-
Carrier-Mediated Transport
- Metabolites/Solute carriers. Facilitated diffusion, secondarily active transporters.
-
ABC Transporters (ATP-binding Cassette)
- Active efflux mechanisms
-
Endocytosis and Transcytosis
- Receptor-mediated or “adsorptive”. Macromolecules.
-
Cellular Diapedesis
- Mononuclear white cells.
What is an important feature of the BBB?
Constant recylcing and production of CSF means that solute levels are tightly regulated by the BBB.
CSF is continually diluted, hence always will have lower conc than the plasma does
Slower things go into the brain, the higher the dilution factor due to CSF turnover
Production and flow fluid in CNS
continual leakage of CSF out into blood
Production
- Choroid Plexuses 60%
- Tissue 40%
Drainage
- Arachnoid villi (granulations)
- Cranial nerves sheathes
- Optic nerve to conjunctiva and nose
- Olfactory nerves, cribiform plate, nasal lymphatics
- Sub-mandibular and cervical lymph nodes
Arachnoid Granulations
Allows fluid out into the blood from the brain, never the other way
- Active 1-way valve
Hydrocephalus
Build up of fluid in the brain
Drainage is not equal to production
Types:
(i) Non-communicating
- blockage of aqueduct of Sylvius
(ii) Communicating
- obstruction of flow in sub-arachnoid space or villi
Consequences:
- huge dilated ventricels
- paralysed extraocular muscles due to increased I.C.P
aqueduct of Slyvius = tube btwn 3rd & 4th ventricle
Foramena of Monro= connects lat vent to 3rd
BBB Permeability
Lipid solubility - MOST IMPORTANT FACTOR
P-glycoprotein
ABC Efflux transportee
Removes harmful stuff from brain and pumps it out into capillaries
Reduces concentration of drugs in brain
*some cancers contain Multridrug resistance-associated proteins which is what makes them them MDR
4th ventricle
Has 3 openings
csf leaks out of these
Arachnoid granulations takes up CSF and excretes into venous sinus and then it goes into the Interal Jugular Vein
