Blood Brain Barrier

Question 1

The BBB is formed by ??? junctions between endothelial cells that line capillaries. these junctions are induced by ??? and prevent passive transfer from the blood into the brain

Answer 1

tight junctions
astrocytes

Question 3

Lipid-soluble substances cross endothelial cells through membranes via ??? diffusion

Answer 3

transmembrane diffusion

Question 4

a substance that is too lipid soluble can be sequestered by the capillary bed and not reach the cells behind the BBB. WHY?

Answer 4

a drug taken up by the membranes that form the BBB must partition into the aqueous environment of the brain’s interstitial fluid to exert an effect

Question 5

BBB has specialised transporters to allow transport of essential water soluble substances such as neurotransmitter precursors and glucose - this is termed ??? transport

Answer 5

carrier mediated transport

Question 6

capillary endothelial cells produce carrier molecules that transport selected essential substances such as ???

Answer 6

glucose, Large amino acids e.g. phenylalanine and neurotransmitter precursors, L-dopa,

Question 7

TRUE or FALSE: carrier proteins are synthesised by capillary endothelial cells and use active transport to transport selected molecules across BBB. Therefore, capillary endothelial cells DON’T contain loads of mitochondria

Answer 7

FALSE THEY DO CONTAIN LOADS

Question 8

pGlycoprotein (P-gp) is also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) and is an ??? transporter

Answer 8

efflux

Question 9

what is an efflux transporter that is highly expressed in the vessel walls of the brain capillaries because of capacity to extrude a large range of compounds from the brain, hence considered to be greatly important for protecting brain from accumulation of potentially toxic substances.

Answer 9

pGlycoprotein AKA multidrug resistance protein 1

Question 10

an efflux transporter is a transporter that moves things ??? cells

Answer 10

out of

Question 11

??? inhibitors are of great interest in pharmacology research as potential avenue to block the efflux of therapeutic agents that are needed to reach the brain.

Answer 11

p-glycoprotein

Question 12

in which disease of the brain is there evidence to suggest that p-glycoprotein is reduced in the brain, resulting in reduced ability to clear amyloid-beta plaques

Answer 12

Alzheimer’s

Question 13

In Amytrophic Lateral Sclerosis (ALS) there is evidence of over-expression of ??? transporters = therapeutic failure of ALS drugs

Answer 13

p-glycoprotein

Question 14

Individuals with the disorder, phenylketonuria (PKU), have mutations in the ??? hydroxylase gene.

Answer 14

phenylalanine

Question 15

??? leads to hyper-phenylalaninemia (i.e. too much phenylalanine in the blood)

Answer 15

Phenylketonuria

Question 16

In PKU, high levels of ??? saturate the LAT-1 amino acid transporter. Tyrosine (dopamine precursor) and tryptophan (serotonin precursor) also use LAT-1 to cross BBB, however in PKU access to LAT-1 is blocked due to excessive ??? = reduction in dopamine & serotonin synthesis in the brain

Answer 16

phenylalanine

Question 17

what disease causes irreversible mental retardation in infants as dopaminergic and serotonin neurotransmitters are critical for normal brain development but are blocked from forming in brain

Answer 17

phenylketonuria

Question 18

phenylalanine is broken down to tyrosine by the enzyme phenylalanine hydroxylase in the ???

Answer 18

liver

Question 19

Phenylketonuria Management includes:
- low ??? diet
- tyrosine supplementation
-Large neutral amino acid (LNAA) supplementation
- kuvan (new drug)

Answer 19

phenylalanine

Question 20

TRUE or FALSE: there are NO places in the brain where the BBB is not present

Answer 20

FALSE there are places where it is not present

Question 21

circumventricular organs refers to the fenestrated regions of the brain, usually located near the ???

Answer 21

ventricles

Question 21

what allows the brain to respond to changes in chemical environment in the remainder of the body and to secrete modulatory neuropeptides into the bloodstream?

Answer 21

having areas of the brain where no BBB

Question 22

??? organs can be secretory (secrete substances directly into the bloodstream) or sensory (sense chemicals in the blood)

Answer 22

circumventricular

Question 23

The hypothalamic median eminence is a ??? that has hypothalamic neurons that release regulating factors which are carried by the portal vessels to the anterior pituitary

Answer 23

circumventricular organ

Question 24

POSTERIOR or ANTERIOR pituitary gland (neurophypohysis) is a circumventricular organ that secretes oxytocin and vasopressin (anti-diuretic hormone) into the circulation

Answer 24

Posterior pituitary gland

Question 25

The ??? gland is a circumventricular organ that secretes melatonin into the blood stream which regulates our circadian rhythm

Answer 25

Pineal

Question 26

Area postrema is known as the “chemotactic trigger zone” (ie vomiting centre). This region senses toxins in the blood and triggers a vomiting reaction in attempt to rid the body of the toxin. Is it a circumventricular organ or not?

Answer 26

it is

Question 27

pathological states that can cause breakdown of BBB:
- Brain infections
- Brain inflammation
- hypertension
- brain ???

Answer 27

tumours

Question 28

Mannitol is a drug that temporarily opens the BBB for 10mins by causing HIGHER or LOWER blood [sugar] in capillaries => draws water out from capillary endothelial cells that line capillary wall = cell shrinkage = no longer joined by tight junctions

Answer 28

Higher

Question 29

TRUE or FALSE: mannitol is a drug that opens the BBB and can cross the BBB

Answer 29

false, it cannot cross BBB

Question 30

the use of focused ultrasound to mechanically disrupt the BBB is achieved by injecting ??? into bloodstream and using ultrasound to vibrate them against BBB = loosening of tight junctions

Answer 30

microbubbles

Question 31

The blood/cerebrospinal fluid (CSF) barrier is formed by the ???

Answer 31

choroid plexus

Question 32

The choroid plexus is located in the ??? and is 3 layered:
- Choroid epithelial cells (ependymal cells)
- Pia mater
- Capillaries

Answer 32

ventricles

Question 33

Choroid capillaries are fenestrated. BUT choroid epithelial cells have tight junctions & prevent flow of blood-born components into ???

Answer 33

cerebrospinal fluid

Question 34

The choroid plexus provides selective or NON-selective (?) flow from blood to CSF

Answer 34

selective

Question 35

??? transport mechanisms transport molecules such as Na+, Cl-, K+, C and B Vitamins (water soluble), across ependymal cells

Answer 35

active transport mechanisms