Blood Brain Barrier Flashcards
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
tight junctions
astrocytes
Lipid-soluble substances cross endothelial cells through membranes via ??? diffusion
transmembrane diffusion
a substance that is too lipid soluble can be sequestered by the capillary bed and not reach the cells behind the BBB. WHY?
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
BBB has specialised transporters to allow transport of essential water soluble substances such as neurotransmitter precursors and glucose - this is termed ??? transport
carrier mediated transport
capillary endothelial cells produce carrier molecules that transport selected essential substances such as ???
glucose, Large amino acids e.g. phenylalanine and neurotransmitter precursors, L-dopa,
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
FALSE THEY DO CONTAIN LOADS
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
efflux
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.
pGlycoprotein AKA multidrug resistance protein 1
an efflux transporter is a transporter that moves things ??? cells
out of
??? 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.
p-glycoprotein
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
Alzheimer’s
In Amytrophic Lateral Sclerosis (ALS) there is evidence of over-expression of ??? transporters = therapeutic failure of ALS drugs
p-glycoprotein
Individuals with the disorder, phenylketonuria (PKU), have mutations in the ??? hydroxylase gene.
phenylalanine
??? leads to hyper-phenylalaninemia (i.e. too much phenylalanine in the blood)
Phenylketonuria
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
phenylalanine
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
phenylketonuria
phenylalanine is broken down to tyrosine by the enzyme phenylalanine hydroxylase in the ???
liver
Phenylketonuria Management includes:
- low ??? diet
- tyrosine supplementation
-Large neutral amino acid (LNAA) supplementation
- kuvan (new drug)
phenylalanine
TRUE or FALSE: there are NO places in the brain where the BBB is not present
FALSE there are places where it is not present
circumventricular organs refers to the fenestrated regions of the brain, usually located near the ???
ventricles
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?
having areas of the brain where no BBB
??? organs can be secretory (secrete substances directly into the bloodstream) or sensory (sense chemicals in the blood)
circumventricular
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
circumventricular organ
POSTERIOR or ANTERIOR pituitary gland (neurophypohysis) is a circumventricular organ that secretes oxytocin and vasopressin (anti-diuretic hormone) into the circulation
Posterior pituitary gland
The ??? gland is a circumventricular organ that secretes melatonin into the blood stream which regulates our circadian rhythm
Pineal
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?
it is
pathological states that can cause breakdown of BBB:
- Brain infections
- Brain inflammation
- hypertension
- brain ???
tumours
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
Higher
TRUE or FALSE: mannitol is a drug that opens the BBB and can cross the BBB
false, it cannot cross BBB
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
microbubbles
The blood/cerebrospinal fluid (CSF) barrier is formed by the ???
choroid plexus
The choroid plexus is located in the ??? and is 3 layered:
- Choroid epithelial cells (ependymal cells)
- Pia mater
- Capillaries
ventricles
Choroid capillaries are fenestrated. BUT choroid epithelial cells have tight junctions & prevent flow of blood-born components into ???
cerebrospinal fluid
The choroid plexus provides selective or NON-selective (?) flow from blood to CSF
selective
??? transport mechanisms transport molecules such as Na+, Cl-, K+, C and B Vitamins (water soluble), across ependymal cells
active transport mechanisms
