Neural Regeneration Flashcards
what is the main environmental difference between CNS and PNS neuron regeneration?
the glial environment
can CNS neurons sprout and make new connections like PNS neurons?
Yes, but glial environment inhibits it
What is the structural difference between CNS and PNS neurons?
there is connective tissue around PNS neurons to help regrowth
PNS neurons have 1 to 1 relationship. CNS is one to many
2 weeks post-injury, what will happen to a PNS neuron
cell soma changes morphology, such that nucleus moves to periphery
loss of Nissl substance, and ribosomes stop working, forming chromolysis
axon breakdown
muscle fibre atrophy
What is Wallerian Degeneration
degeneration of myelin on axon distal to site of injury
debris is cleaned up by macrophages
what happens 3-weeks post PNS injury
Schwann cells proliferation forming a compact cord, guiding axon regrowth
nucleus moves central again
What happens if the regeneration is successful
electrical activity will restore and muscle fibre regenerate
What happens if the regeneration is unsuccessful
neuroma formation, and patient gets unwanted sensation and pain from the bundle of nerve sprouts
Does neuron regenerate faster in a crushed injury? Why?
Yes, faster than having it cut, because the route of connective tissue is still intact. Neurons regenerate better with better alignment
T/F Oligodendrocytes encourage neural growth
False, oligodendrocytes are very inhibitory to regrowth
What is the treatment to primary CNS neural injury
remove primary causative agent to minimise extent of damage
What is an agent used to minimise CNS damage
tissue plasminogen activator (tPA) used in stroke
What are some immediate secondary damage to CNS neurons
degenerative chemical insults in much larger area, including
ischaemia,
Ca influx,
free radical production,
glutamate excitotoxicity (glutamate released but not cleared)
BBB breakdown allow other things to enter
What are some secondary damage that develop in hours to days
immune cell infiltration
microglial activation
inflammatory mediators
What are some secondary damage that develop in days to weeks
axonal degeneration in large area demyelination slow phagocytosis encouraging apoptosis glial scar formation meningeal fibroblast migration (scar)
what are the four potential ways of repairing CNS
protect surviving cells
axonal regeneration with functional integration
modulate astrocytic gliosis
neuron stem cells
Why won’t axons regrow in CNS
lack of trophic factor to guide growth
environment inhibits regrowth
What is trophic support treatment? Why has it stopped
provide growth factors like NGF and BDNF to encourage axonal growth, but it causes neuropathic pain
what is axonal plasticity? How can it be enhanced?
damaged axon retracts, and nearby axon sprouts an extra process to re-innervate
can be enhanced by exercise
What is the cytoskeletal protein of astrocyte that inhibits axonal regrowth? What is its normal role
glial fibrillary acidic protein (GFAP)
helps with neuronal stability
Why can’t we just ablate the astrocytes to prevent glial formation
astrocytes are very important for wound repair. A lack of astrocyte will cause increased inflammation, increased tissue destruction, and BBB repair inhibition
what are the three myelin inhibitor? What do they bind to?
Nogo
Myelin associated glycoprotein
OMgp
all bind to Nogo receptor, resulting in Rho pathway and growth inhibition
What are the two ways of utilising stem cells
mobilise endogenous cells
transplant exogenous cells
where are the endogenous stem cells found
subventricular zone of the lateral ventricle
subgranular zone of the dentate gyrus in hippocampus
where do the cells of subventricular zone go to?
migrate to the olfactory bulb
How can we promote axonal regrowth
by blocking inhibitory molecules and promote axon guidance molecules like Eph
