BBB and Blood CSF Barrier

Question 1

What do the BBB and blood-CSF fluid barrier do for the brain?

Answer 1

1. Protection against oscillations in blood concentrations of metabolites / hormones (e.g. adrenaline)
2. Import of nutrients for brain metabolism
3. Export of products from brain metabolism

Question 2

What are the 3 main components of the BBB?

Answer 2

1. Endothelial cells continuously line the blood vessel
2. Pericytes
3. Astrocytes

Question 3

Why are endothelial cells of the BBB very specialised?

Answer 3

In order to limit passive diffusion of water-soluble (polar) substances from blood

Question 4

How are endothelial cells of the BBB compared to other endothelial cells?

Answer 4

1. Form tight junctions between endothelial cells – act as a very effective wall preventing diffusion between cells.
2. Are not fenestrated – no pores to allow diffusion of molecules and proteins in to cells
3. Relatively deficient in vesicular traffic mechanisms therefore impairing endocytosis

Question 5

Which blood vessels are the exception and are not impenetrable in the BBB?

Answer 5

E.g. Pituitary gland due to secretion of hormones

Question 6

What is the role of tight junctions between endothelial cells in the BBB?

Answer 6

Form protein gate that physically obstructs molecules diffusing through space between cells

Question 7

What are tight junctions made of?

Answer 7

transmembrane proteins: junctional adhesion molecules (JAMs), claudins, occludin and cadherins

Question 8

What is the role of accessory proteins in relation to tight junctions?

Answer 8

link claudin and occludin to actin cytoskeleton , allowing signal transduction and thus (maybe????) regulation of tight junctions

Question 9

Describe BBB permeability

Answer 9

1. O2, CO2 and other small lipophillic molecules can freely diffuse across the endothelial cells down concentration gradients
2. Facilitative and energy-dependent receptor mediated transport of specific polar molecules (e.g. glucose, amino acids (AAs))
3. Ion channels (e.g. K+, Na+)

Question 10

How does lipid solubility affect BBB permeability?

Answer 10

As lipid solubility increases so does permeability

Question 11

Describe why in some cases lipid solubility is not a perfect indicator of BBB permeability

Answer 11

D-glucose,L-leucine, and L-dopa all have higher than expected permeability due to specific channels for them in the BBB.
In the case of anticonvulsants phenobarbital and phenytoin, increased lipid solubility means being insoluble in blood (lower permeability than expected)

Question 12

What is the glucose transporter in the BBB endothelia?

Answer 12

GLUT-1

Question 13

Can glucose move against its concentration gradient through the BBB endothelia?

Answer 13

No, GLUT-1 is a non-energy dependent transporter

Question 14

What occurs with energy source transport into the brain during hypoglycemia?

Answer 14

β-hydroxybutyrate and ketone bodies transported by mono-carboxylic acid transporter 1 (MCT1)

Question 15

How does the brain get amino acids?

Answer 15

They are transported across endothelial cells by transporters

Question 16

How are ions transported through the BBB?

Answer 16

Specific ion channels and transporters mediate electrolyte movement . The Brian side has high numbers of Na+/K+ ATPases to remove extracellular K+ released during neuronal activity.

Question 17

What do ABC transporters do?

Answer 17

They mediate efflux of lipid-soluble molecules out of endothelial cells and thus protect brain by limiting entry of natural and synthetic compounds.

Question 18

Give examples of ABC transporters and their actions

Answer 18

P glycoprotein (PgP) restricts entry of drugs like actinomycin D (chemotherapy drug) and cyclosporin (immunosuppressant)

Question 19

What percentage of brain microvessels do astrocytic end feet ensheath?

Answer 19

99%

Question 20

What channel transports water into and out of the brain and where is it?

Answer 20

aquaporin4 and it is localised to the end feet

Question 21

What percentage of brain micro microvessels are covered by pericytes?

Answer 21

20-30%

Question 22

What kinds of factors do astrocytes and pericytes in the BBB release?

Answer 22

factors that can mediate vasodilation / constriction of blood vessels and increase / decrease permeability of the BBB (e.g. TGF-β, VEGF)

Question 23

What are the functions of the CSF?

Answer 23

1. communicates with brain interstitial fluid helping maintain constant extracellular environment for neurons and glia
2. Allows brain to float acting as mechanical cushion to protect brain from impact with skull
3. pH of CSF affects pulmonary ventilation and cerebral blood flow

Question 24

Describe the CSF

Answer 24

Clear, slightly viscous solution with few cells and about 10 time less protein than blood

Question 25

What is the CSF used to measure?

Answer 25

brain health checked via lumbar puncture (e.g. presence of meningitis, encephalitis; biomarkers of disease)

Question 26

Where is CSF made?

Answer 26

Choroid plexus located in the lateral, third, and fourth ventricles

Question 27

Describe CSF circulation

Answer 27

One-way flow: ventricular system —> spinal canal —> subarachnoid space—> absorbed by subarachnoid granulations

Question 28

What is the purpose of subarachnoid granulations ?

Answer 28

major route for removing potentially harmful brain metabolites

Question 29

Give an idea of the rate of circulation/production of CSF

Answer 29

CSF volume ~ 150 ml

Replaced 3-4 times a day

Question 30

Describe the structure of the choroid plexus

Answer 30

Ependymal cells bound to each other by tight junctions and rest on basal lamina

Question 31

How is the choroid plexus similar to distal and collecting tubes of kidney?

Answer 31

capillary filtration and secretory mechanisms move nutrients, proteins and electrolytes between CSF and blood in both directions

Question 32

Describe the structure of arachnoid granulations

Answer 32

They consist of villi that intrude into the superior sagittal sinus (Basically a giant drainage system running around the top of the head)

Question 33

How do arachnoid granulations drain CSF?

Answer 33

Cells of the villus membrane form vacuoles that transport CSF from one side to the other