B.16 Blood Brain Barrier

Question 1

What is the BBB

Answer 1

• barrier between brain fluid compartments
• barrier between blood and brain extracellular fluids
• shield for concentration level changes elsewhere
  example: changes in blood composition after meal

Question 2

Function overview

Answer 2

If it’s large and charged it can’t get through

1. ion regulation for optimal neural signalling
2. keep cell death low by keeping out toxins, regulating molecular traffic
3. keep proteins out of brain (limits cell proliferation)
4. preserve neurotransmitter signalling separating cns and pas
5. immune surveillance to limit inflammation

Question 3

What is the BBB “made off”

Answer 3

• tight junctions of capillary endothelial cells
• astrocytic foot processes
• Basements membrane
• capillary itself is physical barrier too

Question 4

What can cross the BBB

Answer 4

• lipip soluble components usually (dissolve into lipid membrane of cells)
• very few components can cross
• most drugs cannot cross!!!
• heroin , diazepam can cross (see problem)
• glucose, amino acids can go through for nutrient supply

Question 5

Efflux Transporters

Answer 5

• remove lipid soluble compounds actively
• keeps toxins out
• multidrugresisitant efflux transporter (pgp)

Question 6

What causes BBB breakdown?

Answer 6

-injury
-infection
-trauma
-AD
-Depression
-cerebral Malaria
-Epilepsy
and many more
-> this can then lead to disease progression

Question 7

Consequences of BBB breakdown?

Answer 7

-hyperexcitability through influx of glutamate and calcium
-can lead to excitotoxicity
-changes in potassium levels which can also contribute to depolarisation, change of membrane potentials and hyper excitability (epilepsy)
-

Question 8

Tight Junctions

Answer 8

• specific to brain

- complex protein structure

Question 9

Neurovascular Unit

Answer 9

• communication between astrocytes and capillaries with neuron
• capillaries and neuron connected via astrocytes and pericytes

Question 10

Circumventricular Organs

Answer 10

-some organs do not require BBB
-they need to sample plasma to directly assess changes
OR
-secret factors straight into blood
-they do not have tight junctions
HOWEVER
Junctions through astrocytes so factors cannot enter brain unchecked

Example:

• pineal Body= melatonin hormone into blood
• area postrema= induces vomiting in response to chemical changes in blood
• pituitary: hormones into blood