Exam 2: Neurovascular Flashcards
Neuronal patterning is accomplish by
Axon guidance
guidance cues- receptors on neuron/axon, cue expression from tissue
Chemotaxis
certain tissues expression at certain level/higher gradient. Floorpate of neural tube
hapotaxis
not just gradients, substrates around them (ECM), influecnes axonal guidance
Axons that go long distance travel…
first floorplate, then other things. Down to floorplate, then cross.
Short range cues
contact repulsion/attraction
Long range cues
chemoattraction/repulsion
Example: GTPase Arl13b for cilia regulates ___ signaling.
What happens when you KO guidance cue?
shh signal (Robo3+ axons on sides of neural tube)
Disorganization
Neuronal guidance cues also attract and repeal _____ cells.
What are the two ways they do this?
Endothelial
1) Ligands (secreted by tissue)
2) Recpetors (expressed on ECs)-endothelial cells form lining of blood vessels
how it gets information where effects pattern of vasculature.
Cell mobility:
Vegf, Fgf, Bmp, Apelin, Sdf-1, shh
filopodia extend (actin stress)
polymerize actin, activate integrins, ECM attaches to alpha/beta subunit
Cell mobility:
chordin, noggin, sema3, slit, netrin, ephrin (in’s except apelin)
filopodia retraction
inactivate integrin
depolymerize actin
ECM no bind to alpha/beta
What is the first blood vessel to form in embryonic vascular network?
Dorsal aortae (DA)
Mouse dorsal aortae development
green (endothelial cells) in mesoderm come together and form vessels.
Angioblasts, migrate/consolidate, differentiate, lumen
Avascular zones around dorsal aortae.
DA development: notochord has __ guidance cues
Many
Chordin, noggin, slit2, sema3E, netrin1
How does DA stay where it is?
repulsive neuronal guidance cues in surrounding tissue
What happens to Foxh1-/- mice which lack notochord?
Disorganized dorsal aortae, no repulsion cues.
flkLacZ image
Notochord repels blood vessels, when you remove get ride of
avascular zones, which need Sema3E, also in lateral plate mesoderm by avascular regions.
What happens to Sema3E-PlexinD1 mutant mice
DA pattern is lost
Shared ____ regulate neuronal and vascular patterning
neuronal guidance cues
What s neurovascular reciprocal patterning?
Structures of nerves and blood vessels pattern each other
Nerve –> bv in skin
bv –> nerve in heart
How does neurovascular patterning work in skin?
neuron patterns vascular
physical association
artery forms along nerves
however, VEINS not associated with nerves
What happens to blood vessel patterning when nerves absent (Ngn1-/- and Ngn2-/-)?
blood vessel patterning disrupted
What is the chemoattractant in blood vessels for endothelial cells? (it is responsible for patterning of blood vessels)
VEGF
skin- lots of nerves have VEGF
significantly increases mice lifespan by rejuvenating blood vessels.
What does the retina do?
receive input form light so hits special cells. Light from lens is focus and converted into neuronal signals send to brain.
Blood vessels and astrocytes maintain cell survival.
What is closely associated in retina?
Astrocytes (GFAP) and blood vessels
both requird to pattern each other and maintain function
Astrocytes derived from brain, radially populate retina, and bv do same thing. through optic nerve, branch out
Mice pups are born- what happens to retina blood vessels?
They don’t have any, once born, they come out and radiate. Regulated in part by light.
If pups are kept in the dark, the process is delayed. patterning effect on blood vessels.
Astrocyte derived ____ seems to be patterning blood vessels.
VEGF
What does Sox2 deletion impair?
Retinal astrocyte maturation and subsequently vascular patterning.
KO= less mature patterning
Mature astrocyte
high GFAP, low Pax2
Immature astrocyte
low FGAP, high Pax2
If you KO Sox2, what happens to blood vessels?
Astrocytes not mature, so blood vessels…
process delayed, space doesn’t fill, patterns pretty well, but not good enough, not properly
What labels endothelial cells?
IB4
Do retinal blood vessels regulate astrocyte differentiation?
Yes,
more Mature have more blood vessels
Retina when KO VEGFR-2, vascular defective.
Mature astrocytes move to periphery, vasculature dictates axons.
Shorter distance with defect blood vessels, differentiation zone not extended.
DIFFERENTIATION of axons is off.
upregulation of Pax2 if not a lot of GFAP
How do blood vessels in retina even help astrocyte differentiation?
Oxygen from retinal circulation may promote astrocytic differentiation.
Neurovascular disease:
Wet aged related Macular Degeneration (wAMD) - general information
macula= high concentration of photoreceptors, get light to concentrate to create central vision, color, fine detail
leading cause of vision loss in older Americans
Wet version- new blood vessels grow beneath retina, LEAK BLOOD. causes permanent damage of light-sensitive retina cells, which die off and create blind spots in central vision (anti-VEGF therapies)
Neurovascular disease:
dry AMD
Results from
1) aging and thinning of macular tissues
2) deposition of pigment in macular (drusen)
3) combination of 1 and 2
Neurovascular disease:
Stroke- general
Sudden interruption in blood supply, brain can’t get oxygen and nutrients
SYMPTOMS: paralysis/loss of muscle movement Difficultly talk/swallow memory loss/thinking difficulties Emotional problems Pain Changes in behavior/self-care ability
Neurovascular disease:
Ischemic stroke cause
blocked artery
Neurovascular disease:
Hemorrhagic stroke
leaking or bursting blood vessel
Neurovascular disease:
Brain aneurysm
bulge in blood vessel of brain leaks/ruptures, causing bleeding in brain
increase pressure in skull. Too much pressure, blood and oxygen supply to brain may be disrupted to the point that loss of consciousness and death occur
Neurovascular disease:
Arteriovenous malformation (AVMS)
Name the 2 forms
Fragile, inappropriate connections between arteries, and veins that are prone to hemorrhaging, which can lead to stroke and death
1) Familial forms- lung, liver, and brain
2) Sporadic forms
Familial: primary view capillaries what is wrong, bv too dilated, shunts between them.
Neurovascular disease:
Vasculties
inflammation of blood vessels
Changes in blood vessels walls, thickening, weakening, narrowing or scarring. Can be CNS or PNS, depends on location.
Neurovascular disease:
Vasculitis symptoms
Vary by location
Aneurysms (hemorrhagic stroke) Blood clots (ischemic stroke)
Confusion or forgetfulness (dementia) Sensation abnormal Muscle weakness/paralysis- arms/legs Swelling of brain Vision problems Seizures and convulsions Trouble speaking or understanding
