lecture 4 Blood Brain Barrier Flashcards

1
Q

Blood–CSF barriers

A

Choroid plexus epithelial cells

Arachnoid membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Choroid plexus is

A

main site of entry for Ca2+ into the brain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the blood-brain barrier

A

A highly selective semi-permeablebarrier separating the circulating blood from the brain and spinal cord

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

types of cells that make up BBB

A

Brain endothelial cells, basement membrane, pericytes, astrocytes, neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

_________ cells that precludes entrance of

substances into the brain

A

tight-junctioned brain capillary

endothelial

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

BBB has gaps where

A

in some sensory (area postrema) and secretory area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

______ are responsible for the formation and the maintenance of the BBB

A

Astrocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the main Cellular constituents of the BBB (%)

A
Brain endothelial cells
Basement membrane
Pericytes
Astrocytes
Neurons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

fenestrations occur in

A

periphery (a gap)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

TJs are one mode of cell-cell adhesion, sealing the ________ between endothelial cells.

A

aqueous paracellular diffusional pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Linked together by a complex of proteins which span the inter-endothelial space creating

A

Tight Junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Individual TJ strands then ____ and tightly associate with strands in the apposing membrane of _____to form paired strands, intercellular distance becomes nonexistent….. “kissing points

A

laterally,,adjacent cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the 4 main the interaction between integral membrane proteins

A

Junctional Adhesion Molecules
Occludin
Claudin
Adherence Junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Junctional Adhesion Molecules with a single transmembrane domain, was shown to associate laterally with TJ strands, but

A

not to constitute the strands per se

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Zonulae Occludins are ____conditions where BBB breakdowns and TJ can formed wit/without

A

decreased without

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Adherens Junctions______ found in many tissues

A

Adhesive cell-cell contact

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

3 main functions of BBB important

A

Physical:BECs & tight junctions
Transport: Specialized transporters
Metabolic: enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Cadherin dimers form

A

cell-cell adhesion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

____is critical for the normal functioning of cadherins, which have a _____ binding site in their extracellular domain

A

calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

_____ is a major constituent of TJ strands

A

Claudin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Experiment: WT and Cldn 5-/- embryos injected with a

low molecular mass tracer Findings and authotrs hypothesis

A

WT mice had no tracer from CNS, whereas
Cldn 5-/- mice showed had tracer throughout CNS parenchyma
Authors hypothesis: BBB is loosened in a size-selective manner in Cldn 5-/- mice.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Main molecular traffic routes across the BBB

A

1) Transcellular Diffusion
2) Transport Proteins
Solute Carriers
ABC Efflux Transporters
3) Trancytosis
Receptor-mediated
Adsorptive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Transcellular diffusion is dependent upon

A

lipid solubility-High oil/water partitioning coefficient (K)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

But NSAIDs, like aspirin, are structurally lipophilic. Why does it have low lipid solubility on this graph?

A

The majority of NSAIDs circulate as organic anions (at physiological pH). Such that the small neutral (un-ionized) fraction may prove limiting to brain uptake.

25
Q

Facilitative transporters: allow

A

solutes to flow downhill with their electrochemical gradient

26
Q

Facilitative transporters: example

A

. Cationic amino acid system (Y+) Lysine, arginine, and ornithine

27
Q

Secondary active transporters:

A

Ion-coupled transporters and exchangers that do not require ATP

28
Q

ATP-binding cassette (ABC) efflux transporters are located where

A

Located on luminal membrane of the BBB

29
Q

ATP-binding cassette (ABC) efflux transporters function

A

Use ATP to actively eject a range of substances, including both xenobiotics and endogenous TOXIC molecules

30
Q

Trancytosis (Receptor-mediated) Primary route of transport for…

A

essential peptides and signaling molecules

Including insulin, leptin, and transferrin

31
Q

Trancytosis (Receptor-mediated Requires ligand-receptor binding, followed by

A

by endocytosis and exocytosis

Ex. Iron-bound transferrin

32
Q

Trancytosis (Adsorptive-mediated) Primary route of transport for…

A

Primary route of transport for many plasma proteins

Ex. Albumin

33
Q

Trancytosis (Adsorptive-mediated) what types of molecules are readly absorbed

A

Cations b/c BECs carry an overall negative surface charge on their luminal membrane due to heparan sulfate proteoglycans

34
Q

BBB is formed via complex interactions between (what types of cells) and the basement membrane

A

endothelial cells, astrocytic endfeet, pericytes

35
Q

5 molecular routes across the BBB exist

A

Transcellular diffusion, solute carriers, ABC efflux transporters, and transcytosis (receptor mediated and adsorptive)

36
Q

BBB breakdown may occur in

A

many neurological diseases

37
Q

_______ as well as finding novel ways to disrupt the barrier to allow for penetration of said drugs, is a hurdle facing scientists today

A

Developing new drugs to cross the BBB,

38
Q

Trancytosis (Receptor-mediated Requires

A

endocytosis and exocytosis only No receptor required -

39
Q

BBB acts as as an enzymatic barrier by

A

Allows for uptake of neurotransmitter precursors

L-DOPA

40
Q

Basement membrane / basal lamina Surround ____ and provieds _______

A

BECs, and structurral support

41
Q

what can bind to the BM via specific receptors

A

BECs, astrocytes, and pericytes

42
Q

Basement membrane is made of

A

Composition: mixture of different extracellular matrix proteins

43
Q

Pericytes Named with respect to their

A

unique localization in the perivascular space of brain vessels

44
Q

murual cells aka

A

Pericytes

45
Q

pericyte : BEC ratio

A

1:5

46
Q

pericyte Functions include:

A

Vessel formation, sprouting, and stabilization

Vessel diameter and CBF

47
Q

Cross-talk and functional coupling between ___&____ is the result of several signal transduction cascades

A

pericytes and BECs

48
Q

neural scars are formed by

A

pericytes and astrocytes

49
Q

Pericytes Essential for ___ (4) during angiogenesis

A

recruitment, proliferation, migration, and attachment

50
Q

Pericyte-deficient mice

A

Accumulation of intravenously injected tracers in the brain parenchyma and endothelium

51
Q

Perivascular endfeet of _____ surround BECs and are contiguous with the basal lamina

A

astrocytes

52
Q

____ channel, involved in ion and volume regulation

A

Aquaporin 4 (AQP4) and Kir4.1 K+

53
Q

Weakening of the blood-brain barrier may precede, accelerate, or contribute to a number of

A

neurodegenerative diseases

54
Q

Examples: BBB breakdown

A

MS and infiltration of white blood cells, which go on to attack myelin
Stroke, epilepsy

55
Q

uptake of “vital dye” into parenchyma in ____ epileptic mice

A

increased

56
Q

BBB Dysfunction may occur via ABC transporter _______

A

overexpression

57
Q

Crossing the BBB Administration of

A

hyperosmolar agent

58
Q

Crossing the BBB Receptor-meditated transcytosis thought of as

A

Trojan-horse method

59
Q

Magnetic resonance-guided focused ultrasound helps

A

Locally disrupts BBB, therapeutic agents can be loaded into MBs