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BPS 2nd part > Blood Brain Barrier > Flashcards

Blood Brain Barrier Flashcards

1
Q

Who, when and how the impermeability of the BBB was first established?

A
  • Edwin Goldman
  • 1913
  • Injected dye in rats outside of the brain + injected dye in rats in the brain
  • Dye never crossed into or out of brain – conclusion … bbb
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2
Q

Illustrate the molecular structure of the tight junction in the brain endothelial cells (+ 3 proteins)

A

IN NOTES

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3
Q

Identify 3 specific proteins associated with the BBB

A
  1. Claudin
  2. Occludin
  3. Adherin junctions
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4
Q

List and explain the principle of FOUR drug-delivery strategies that scientists have explored to improve drug delivery across the BBB

A
  1. Absorption occurs between (-) charges
    - can alter albumin or therapeutic drugs to have more (+) charges
  2. Membrane receptors
    - can be fooled with ligands that are complexed with drugs
    - endocytosis can occur
  3. Active efflux
    - this can be inhibited to enhance intracellular retention of drugs
  4. Passive diffusion
    - improved by increased lipophilicity (hydro)
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5
Q

Explain the mechanism by which EDTA could increase the permeability of the BBB to drugs

A

EDTA coordination complex can bind with Ca2+ (acts as s calcium chelator) – this loosens the tight junctions and allows paracellular diff
- removes Ca2+ and destabilizes ionic reaction

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6
Q

Blood-Brain Barrier

A
  • Extremely selective filter that coats the blood vessels in the brain, preventing harmful substances in the bloodstream from passing through
  • Found between blood and the CNS
  • Two component system ( blood-CSF barrier and blood-brain barrier) –> diffusion of drugs are prevented by both BBB and BCB
  • BBB formed by endothelial cells
  • signals come from neurons and cells
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7
Q

Vascular endothelial cells

A

Lines blood vessels

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8
Q

Tight junctions

A
  • Tight junctions impede the passage of macromolecules

- seal adjacent epithelial cells in a narrow band just beneath their apical surface

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9
Q

Neurovascular unit

A
  • BBB components and neurons that are essential for the health and function of the CNS
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10
Q

Paracellular diffusion

A
  • transfer of substances across an epithelium by passing through the intercellular space between the cells (no tight junctions)
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11
Q

Amyloid beta + Alzheimers

A
  • Amino acids that are involved in Alzheimer’s disease
  • The main component of the amyloid plaques found in the brains of Alzheimer patients
  • In Alzheimers, plaque buildup is due to disfunctional BBB (initially caused by several factors which causes AB secretion and in turn influx into brain)
  • diabetes can also lead to Alzheimers
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12
Q

Absorptive mediated transcytosis

A
  • binding of substances to the negative charges on the BBB PM
  • This is where endocytosis occurs
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13
Q

Membrane receptor

A

Proteins that are located on the plasma membrane and can transmit a signal when a ligand is bound it it.

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14
Q

Celebrospinal fluid (CSF)

A
  • acts like a cushion/buffer for brain’s cortex

- provides basic mechanical and immunological protection to the brain

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15
Q

Two features of brain endothelial cells

A
  1. LOTS of Tight junctions

2. Lil amt of caveolae

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16
Q

Caveolae

A
  • membrane bound vesicles involved with endocytosis and transcytosis
  • 14 fold less caveolae than in non neural
17
Q

Gate barrier function of tight junctions

A
  • junctions are made of continuous strands that extend circumferentially around the endothelial
  • prevents movement of molecules to go in between cells (paracellular)
18
Q

Fence barrier function of tight junctions

A
  • restrict the movement of membrane molecules between the functionally distinct apical and basal sides
19
Q

Tight junction- claudin and occuldin characteristics

A
  • loops + overhangs
  • overhangs interact with linker proteins attached by cytoskeleton
  • can essentially be loosened
20
Q

Adherins junctions

A
  • stabilize cell adhesion and limit any paracellular diffusion
  • located below tight junctions
  • ionic interaction between cadherins (meant to stabilize cell interaction) which makes it possible to interfere with
21
Q

Brain injury

A

BBB breakdown –> no tight junctions –> angiogenesis + restoration

  • trauma related to BBB disfunction
  • entry of K+ or albumin into BBB results in seizures
22
Q

Occudin

A
  • contributes to fence and gate
  • key anchorage site for actin cytoskeleton
  • determines cell fate and development
23
Q

Claudins

A
  • determine the tissue, charge and size selectivity of the paracellular seals
  • most important in preventing anions and cations from diffusing through

BPS 2nd part (2 decks)

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