Blood-CNS barrier Flashcards
Where is the level of the BBB
At the level of the capillaries
What is the capillary density of the brain
2500 - 3000 /mm3
What are the functions of astrocytes
1) energy and nutrient support (there’s an astrocyte between each capillary and neuron
2) ion and water homeostasis
3) termination of synaptic activity
4) maintenance of the BBB
5) breathing regulation
What are the proteins involved in the tight junctions between the cerebellar endothelial cells
Claudin 3,5,12 + Occuldin
JAMs (junctional adhesion molecules) + ESAM (endothelial selective adhesion molecule)
What are the proteins involved in the adherens junctions
PECAM = platelet endothelial cell adhesion molecule VE-cadherin = vascular endothelial cadherin
What is the trans-endothelial electrical resistance in normal body cells vs that at the BBB
2-20 ohms/cm3
vs
>1000 ohms/cm3
What affect does lipophilicity have on uptake through the BBB
Increasing lipophilicity increases uptake across the BBB; its a lipid bilayer
Why is heroin so good
Its v lipophilic so its uptake across the BBB is quite high, then when it reaches brain tissue it is metabolised to morphine, but because morphine is hydrophilic is it trapped in the cells and the effects last longer
Describe AA uptake across the BBB
AAs sorted into groups based on similar charge/size
Some transporters are polarised ie they are only on one membrane
Describe P-glycoprotein pharmacology
A receptor in endothelial cell membrane of BBB; has 12 transmembrane domains and 2 binding sites, both within the lipid bilayer therefore only lipophilic drugs bind there
Describe the process of selective endocytosis
A substrate binds to a receptor on the outside of the membrane, then a vesicle forms around the receptor and it is deposited on the other side of the cell and released from the receptor
What are the functions of the BBB
Controls molecule influx into brain ISF
Supplies brain w/ essential nutrients
mediates efflux of waste products
restricts ionic and fluid movements
What produces the CSF
choroid processes
What do the choroid processes do
produce CSF, synthesises polypeptides, contributes to regulation of the brain
Describe the physiology of the CSF ionic secretion
On the apical membrane there is a protein that moves Cl- ions into the cell and moves HCO3- ions out, then there is another protein which moves Na+ ions in to the cell and H+ ions out of the cell. There are also AQP1 proteins on both membranes for the movement of water.
Then on the basolateral membrane there is a Na+/K+ ATPase which moves K+ into the cell; there is also a Na+/2Cl-/K+ co transporter which moves ions out of the cell into the CSF.
Carbonic anhydrase is also active inside the cell
