Blood Brain Barrier BBB Flashcards
TJs
tight junction molecules
connecting endothelial cells
transmembrane proteins like claudin and occludin
control in- and outflow
adherence junctions
connect cells more loosely
cadherin proteins
Want pathway
for development and tissue regeneration
angiogenesis
(re)generation of blood vessels
transcytosis pathway
transferring nutrients to brain
taken up by transporters
to not break down & not touch the lysosome
ABC transporter
= ATP binding cassette
basic transmembrane transporters
using ATP
transferrin pathway
brings protein through membrane
binds and brings to brain
nanoparticles
e. g. liposomes
small artificial vesicle
one lipid bilayer
for drug administration
focused delivery
bubbles injected in brain
popped by ultrasound
opening up BBB focally
for drug administration
BBB dysfunction consequences
leakage of neurotoxic serum
lack of nourishment
inflammation
loss of pericye contacts
cerebral amyloid angiopathy
amyloid deposits in vasculature
capCAA
capillary amyloid angiopathy
increased microvascular density in CAA
mediated by ANGPTL-4
increasing vessel sprouting
TDP-43
mutation in 30% of FTD cases
cleaves progranulin to granular
growth factor associated with wound healing
impaired
MS cause
erroneous autoimmune response
T helper cells 1 and 17 infiltrate brain
as well as monocytes
how do immune cells get into MS brain
roll on endothelial cells
adhere and communicate
transmigrate through membrane
start attacking myelin
MS symptom phases
relapsing-remitting phase with inflammatory bouts
(linearly) progressing MS
MS postmortem slices
PLP myelin protein absent in lesions
MHC class II high prevalence
Natalizumab
blocks VLA4
decreases cell migration into brain
some patients died by endogenous brain virus
because suppressing whole system was repressed
LXR
liver X receptor
nuclear
unregulates NFkappaB
pro-inflammatory
agonists in strokes
antagonists in MS
CSF in MS
normally neuroprotective
impaired barrier function in MS
T cell accumulation
blood meningeal barrier
accumulation of immune cells in MS
clusters leak out inflammatory signals
B cells outside activate microglia in brain
