Neural Regeneration Flashcards
central axon damaged what happens? 3 things
Retract processes
Sprouting possible
inhibited by glial scar
how does the PNS neuron look after nerve injury?
- peripheral nucleus
2. loss of Nissl substance
what is chromolysis/chromatolysis?
loss of Nissl substance
What is Wallerian Degeneration?
degen of axon/myelin below injury, mopped up by Macrophages
3 weeks post injury to PNS what do you get?
schwann cells proliferate, compact cord
How fast do PNS axons regrow?
0.5-3mm/day
how long for successful regen in PNS since initial injury?
~3months
How does the regenned PNS nerve look compared to normal?
thinner sheath
what happens if you get unsuccessful PNS regen?
neuroma formation
Repair in PNS is faster when?
crushed vs. cut
main therapeutic approach to PNS injury?
microsurgery
oligodendrocytes and CNS regen do what?
inhibit regrowth
secondary damage minutes to hours in SCI include 5 things:
- ischemia
- Ca2+ influx
- lipid peroxidation/free radicals
- glutamate excitotoxicity
- BBB break down
Treatment for SCI degenerative insults?
erythropoietin
Hours to days/weeks what happens in SCI? what happens? 3 things?
immune cells infiltrate
microglia activate
cytokines/chemokines released
what is a syrinx?
cavity formation for meningeal fibroblasts in SCI
What in the injury environment inhibits CNS regen? 2 big things things
astrocytic gliosis
Glial scar
4 things needed to repair CNS?
- Neuroprotection
- Axononal regen/functional integration
- modulate astrocytic gliosis
- neural stem cells
2 approaches to neural stem cells are?
- mobilise endogenous cells
2. transplant exogenous cells
Another reason for lack of CNS regen besides injury environment?
lack of trophic support
no growth promoting factors
what is sprouting?
an adjacent nerve grows new processes to take over injured nerve’s functions
Astrocytic gliosis does what?
increase GFAP
cytokines
extracelular matrix, proteogylcans
becomes glial scar = barrier to regen
research to prevent Astrocytic gliosis?
blocking extracellular matrix
what happens if you knock out astrocytes completely in an SCI?
no regen at all
approach for Astrocytic gliosis?
regulation
block inhibitors secreted by astrocytes
What is Nogo? treatments?
Myelin inhibitor
testing anti-Nogo
What are axon guidance molecules?
promote, repel or guid regrowing axons
What does Nogo receptors activate?
Rho signalling = inhibits axon regrowth
What are Eph/Ephrins?
possible axon guidance molecules
What does Rho kinase in SCIs do?
activates astrocytes inhibiting regrowth
CNA vs. PNS degen?
CNS: slow
PNS: quick
CNA vs. PNS nerve structure after injury?
CNS: destroyed
PNS: intact
Schwann cells do what to injured PNS?
supports axon regrowth
What are the two main regions of neural stem cells?
- subventricular zone (lateral ventricle)
2. subgranular zone (hippocampus)
Problems with endogenous neural stem cells in SCIs? 4:
- Proliferation
- migration (blocked by inflamm/gliosis
- differentiation
- Survival
what are iPSC and ESC?
induced pluripotent stem cell
embryonic stem cell
what kind of therapy is likely for SCI Rx?
combination
How to help with functional regen?
physical therapy
3 myelin proteins are? what do they do?
Nogo
MAG: myelin-associated glycoprotein
OMcp: oligodendrocyte myelin glycoprotein
bind to NogoR = inhibit regen
name 4 kinds of upregulated axon guidance molecules:
- semaphorins
- tenascin
- cell adhesion molecules (N-CAM, L1, N-Cadherin)
- EphA4/ephrinA5
