Blood-Brain-Barriere

Question 1

main cells that support the BBB

Answer 1

astrocytes

Question 2

waar zitten de astrocyten aan vast?

Answer 2

aan de endothelial cells van de vessles

Question 3

pericytes

Answer 3

smooth muscular cells

Question 4

what is the physical barriere

Answer 4

door tight junctions, houden moleculen tegen om niet in de vascular tract te komen van het brein

Question 5

door TJ komt …

Answer 5

selected transport across the BBB

Question 6

what drugs can enter?

Answer 6

small, unbound, lipophilic drugs.

However, after passing through the barrier the molecule must be hydrophilic enough to move through the interstitial brain fluid to reach the brain.

Question 7

wat voor drug deliveries are possible?

Answer 7

1. intranasal delivery
2. nanoparticles
3. focused ultrasound
4. convection enhanced delivery (catheter)
5. intra-arterial delivery

Question 8

BBB dysfunction in…

Answer 8

MS, AD etc

Question 9

pathological events in MS

Answer 9

demyelination
impaired BBB function
immune cell trafficking
gliosis
neurodegeneration

Question 10

gliosis

Answer 10

change in astrocytes and microglia

Question 11

cns glial cells

Answer 11

astrocytes, microglia, oligodendrocytes, radial glial cells, and ependymal cells.

Question 12

consequences of BBB dysfunction

Answer 12

• Neurotoxic compounds in CNS
• Lack of nourishment
• Endothelial inflammation -Immune cell entry
• Activation of microglia and astrocytes
• Loss of pericyte contacts

Long term effect:
•Neurodegeneration
•Cognitive impairment

Question 13

how does the immune response gets activated

Answer 13

inflamed endothelium attracts immune cells -> immune cell migration

Question 14

natalizumab werking

Answer 14

prevents the leukocytes from crossing the BBB -> geen immuneresponse die het myeline gaat aanvallen.
It blocks one of the molecules on the leukocytes → integrin PLA 4. By doing that, the leukocyte cannot longer interact with the endothelial cells

Question 15

natalizumab en JC virus

Answer 15

Natalizumab treatment is associated with the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic brain infection that is caused by the JC virus

Question 16

3 brain barrieres

Answer 16

blood brain barriere
meninges
choriod plexus

Question 17

wat is de choroid plexus

Answer 17

De plexus choroideus is een onderdeel in de hersenen, waar hersenvocht aangemaakt wordt.[1] Dit gebeurt op plekken waar de pia mater en de weefselwand met elkaar in contact komen. Deze gebieden liggen aan de rand van de hersenventrikels.

Question 18

wat voor barriere maakt de choroid plexus dus?

Answer 18

een bloed-csf barriere

Question 19

wat is er mis in MS met de choroid plexus/

Answer 19

alterations in transcriptome

Question 20

wat gebeurt er dus bij de CP in MS?

Answer 20

Impaired epithelial barriere function
Loss of neuroprotective function
Epithelial inflammation
T cell accumulation and activation

Question 21

meninges barriere in MS fout?

Answer 21

Accumulation of B cells
Microglia activation
neurodegeneration
ocrelizumab targets B cells -> potential MoA

Question 22

Dus de 3 barrieres en wat er mis gaat in MS:

Answer 22

blood brain barriere -> BBB alterations, inflammation, immune cell trafficking

choroid plexus -> T cell infiltration, loss of neuroprotective function

meninges -> B cell infiltration, microglia activation, neurodegeneration