1. Cell attachment 2. cell migration 3. barrier to passage of macromolecules

3. Blood Brain Barrier Flashcards by Victor Peng

If a water-soluble dye is injected in the blood, does it cross into the brain at all? If so, which area?

No penetration from the blood into the brain EXCEPT for the CHOROID PLEXUS

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Is there a gap between the astrocytic endfeet and the outside of the blood vessel?

Yes, gap is ~20nm

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Blood/brain barrier is a barrier between blood and what? What structure is responsible?

Extracellular fluid

Endothelium

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Blood/CSF barrier is a barrier between blood and CSF. Where?

Tight ependymal junctions (tight junctions, epithelium)

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CSF/Brain barrier is a barrier between CSF and what?

Which level?

Extracellular fluid

Leaky ependymal junctions (epithelium)

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Are dura mater blood vessels fenestrated or non-fenestrated?

They are fenestrated –> fluid can pass from endothelial cells into extracellular space with enough pressure

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Are arachnoid and pia mater blood vessels fenestrated? Give the three important characteristics of blood vessels in this region that make up the BBB

Nonfenestrated with tight junctions
Lack pinocytic vesicles
Endothelium is selectively permeable

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What is the name given to the perivascular space that exists around the arterial branches that penetrate the brain?

Virchow Robin space

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What surrounds the endothelial cells and pericytes?

Basal lamina

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5 components of bassal lamina

laminin
fibronectin
tenascin
collagen
proteoglycans

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Fx of basal lamina

Cell attachment
cell migration
barrier to passage of macromolecules

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What do pericytes do?

Regulate proliferation, survival, migration, differentiation, and branching

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Are pericytes phagocytic?

Yes, pericytes are phagocytic

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T/F Gap junctions are present between pericytes and endothelial cells, also present between astrocytes and endothelial cells.

True

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What do astrocytes do?

Help with BBB function
Survey and identify what is coming and going through barrier
Guide neuronal migration and vessel migration during development

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What does the BBB restrict?

Passage of high-charged molecules, large molecules, low lipid soluble molecules, and toxins/drugs

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Between which cells are tight junctions present in the BBB? Purpose of them?

Between the endothelial cells.

Purpose is to maintain high electrical resistant barrier, not let much through (low paracellular permeability)

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What kind of junctions are present between two endothelial cells?

Gap junctions, tight junctions (zonula occludens), and zonula adherens

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What are the three important proteins found in tight junctions?

Occludins, claudins, zonula occludins (ZO1, 2, 3)

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Which protein in tight junctions acts as the primary seal?

Cluadins

What is the function of ZO1,2,3? What can they bind to?

Act as recognition proteins for tight junctional placement

Occludins, cytoskeleton, kinases, signal transcution proteins

What are JAMs and where are they found?

JAMS are members of immunoglobulin superfamily

Found in tight junctions

What happens in infants and newborns if unconjugated bilirubin crosses the BBB?

Kernicterus

unconjugated bilirubin is toxic to brain tissue. Barrier not as good in infants

Endothelia in the brain have more _________ because they require more active transport

mitochondria

Which enzymes are located in endothelial cells? Purpose of having these enzymes?

1. gamma glutamyl transpeptidase 2. alkaline phosphatase 3. aromatic acid decarboxylase Metabolizes drugs, nutrients, neuroactive blood-borne substances

Are peripheral capillary walls thinner than brain capillary walls?

No, brain caps are actually thinner to allow for shorter transport time

Difference between subdural and subarachnoid/pia capillaries

Subdural caps are fenestrated and do not have tight junctions Subarachnoid/pia caps are not fenestrated and have tight junctions

T/F There is polarity between the two sides of the endothelial cell in BBB

True. Polarity exists between the luminal and abluminal surfaces

Two major pathways for transport on BBB

Lipid mediation, catalyzed transport

Lipid mediation transport w/ BBB

Lipid solubility --> passive diffusion | Small lipid molecules and most drugs get through

How is CHO/acid metabolic substrates transported in brain?

Through carrier mediated facilitated transportation

How are vitamins and ions transported?

Active transport, catalyzed

Which occurs faster: Carrier mediated transport vs receptor-mediated transport

Carrier mediated transport occurs in msec | Receptor-mediated transport occurs in mins

What are the two main components of the Blood/CSF barrier (choroid plexus)

Fenestrated choroidal capillaries | Tight junctions between choroidal epithelium

Does the choroid plexus reabsorb CSF? Why?

Yes. Remove metabolites from CSF for venous drainage; monitor CSF composition

Are the choroidal capillaries leaky or not?

They are leaky to allow for molecules that will become part of CSF

Is CSF/brain barrier leaky? What happens with age? Why is it leaky?

Yes, leaky ependymal wall of ventricles. Barrier diminshes with age Free exchange between the CSF and brain intersitital fluid down concentration gradients

What are circumventricular organs (CVO)?

Places in brain where there isn't BBB present; brain structures with direct contact with peripheral blood for monitoring and function

Where are the CVOs present?

``` POSS MAN P: pineal gland O: organ vasculosom of lamina terminalis (OVLT) S: Subfornical organ S: Subcomissural organ ``` M: Median eminence A: Area postrema N: Neurophysis

Area postrema fx

emetic center of brain, causes emesis w/ noxious substance consumption

Subfornical organ location and fx

Below fornix | Thermoregulation, deitary response, communication with hypothalamus, wakefulness

How quickly does heroin/morphine uptake into brain?

Crosses BBB very quickly; 68% uptake into brain w/in 30

Therapy of Parkinson's disease

L-DOPA (precursor to dopamine) Must give amino acid decarboxylase inhibitor to prevent peripheral conversion of L-DOPA to dopamine (inhibitor doesn't cross BBB)

What can you use to decrease intracranial pressure?

Mannitol; hyperosmotic - draws water from endo cells to open BBB

RMP-7

Receptor mediated permeabilizer; deliver carboplatin as chemotherapeutic for brain tumors

Tx for tardive dyskinesia

DHA with dopamine

Tx for multiple sclerosis

Flavonoids, act as anti-oxidants for neuroinflammotory response; can cross BBB

Brain targetor concept

Drug linked to lipohilic targetor that allows conversion to hydrophilic form in the brain --> locks drug into brain Prevents peripheral effect of drug