BBB and Blood CSF Barrier Flashcards
What do the BBB and blood-CSF fluid barrier do for the brain?
- Protection against oscillations in blood concentrations of metabolites / hormones (e.g. adrenaline)
- Import of nutrients for brain metabolism
- Export of products from brain metabolism
What are the 3 main components of the BBB?
- Endothelial cells continuously line the blood vessel
- Pericytes
- Astrocytes
Why are endothelial cells of the BBB very specialised?
In order to limit passive diffusion of water-soluble (polar) substances from blood
How are endothelial cells of the BBB compared to other endothelial cells?
- Form tight junctions between endothelial cells – act as a very effective wall preventing diffusion between cells.
- Are not fenestrated – no pores to allow diffusion of molecules and proteins in to cells
- Relatively deficient in vesicular traffic mechanisms therefore impairing endocytosis
Which blood vessels are the exception and are not impenetrable in the BBB?
E.g. Pituitary gland due to secretion of hormones
What is the role of tight junctions between endothelial cells in the BBB?
Form protein gate that physically obstructs molecules diffusing through space between cells
What are tight junctions made of?
transmembrane proteins: junctional adhesion molecules (JAMs), claudins, occludin and cadherins
What is the role of accessory proteins in relation to tight junctions?
link claudin and occludin to actin cytoskeleton , allowing signal transduction and thus (maybe????) regulation of tight junctions
Describe BBB permeability
- O2, CO2 and other small lipophillic molecules can freely diffuse across the endothelial cells down concentration gradients
- Facilitative and energy-dependent receptor mediated transport of specific polar molecules (e.g. glucose, amino acids (AAs))
- Ion channels (e.g. K+, Na+)
How does lipid solubility affect BBB permeability?
As lipid solubility increases so does permeability
Describe why in some cases lipid solubility is not a perfect indicator of BBB permeability
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)
What is the glucose transporter in the BBB endothelia?
GLUT-1
Can glucose move against its concentration gradient through the BBB endothelia?
No, GLUT-1 is a non-energy dependent transporter
What occurs with energy source transport into the brain during hypoglycemia?
β-hydroxybutyrate and ketone bodies transported by mono-carboxylic acid transporter 1 (MCT1)
How does the brain get amino acids?
They are transported across endothelial cells by transporters
How are ions transported through the BBB?
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.
What do ABC transporters do?
They mediate efflux of lipid-soluble molecules out of endothelial cells and thus protect brain by limiting entry of natural and synthetic compounds.
Give examples of ABC transporters and their actions
P glycoprotein (PgP) restricts entry of drugs like actinomycin D (chemotherapy drug) and cyclosporin (immunosuppressant)
What percentage of brain microvessels do astrocytic end feet ensheath?
99%
What channel transports water into and out of the brain and where is it?
aquaporin4 and it is localised to the end feet
What percentage of brain micro microvessels are covered by pericytes?
20-30%
What kinds of factors do astrocytes and pericytes in the BBB release?
factors that can mediate vasodilation / constriction of blood vessels and increase / decrease permeability of the BBB (e.g. TGF-β, VEGF)
What are the functions of the CSF?
- communicates with brain interstitial fluid helping maintain constant extracellular environment for neurons and glia
- Allows brain to float acting as mechanical cushion to protect brain from impact with skull
- pH of CSF affects pulmonary ventilation and cerebral blood flow
Describe the CSF
Clear, slightly viscous solution with few cells and about 10 time less protein than blood
What is the CSF used to measure?
brain health checked via lumbar puncture (e.g. presence of meningitis, encephalitis; biomarkers of disease)
Where is CSF made?
Choroid plexus located in the lateral, third, and fourth ventricles
Describe CSF circulation
One-way flow: ventricular system —> spinal canal —> subarachnoid space—> absorbed by subarachnoid granulations
What is the purpose of subarachnoid granulations ?
major route for removing potentially harmful brain metabolites
Give an idea of the rate of circulation/production of CSF
CSF volume ~ 150 ml
Replaced 3-4 times a day
Describe the structure of the choroid plexus
Ependymal cells bound to each other by tight junctions and rest on basal lamina
How is the choroid plexus similar to distal and collecting tubes of kidney?
capillary filtration and secretory mechanisms move nutrients, proteins and electrolytes between CSF and blood in both directions
Describe the structure of arachnoid granulations
They consist of villi that intrude into the superior sagittal sinus (Basically a giant drainage system running around the top of the head)
How do arachnoid granulations drain CSF?
Cells of the villus membrane form vacuoles that transport CSF from one side to the other
