Neural Regeneration Flashcards

1
Q

central axon damaged what happens? 3 things

A

Retract processes
Sprouting possible
inhibited by glial scar

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2
Q

how does the PNS neuron look after nerve injury?

A
  1. peripheral nucleus

2. loss of Nissl substance

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3
Q

what is chromolysis/chromatolysis?

A

loss of Nissl substance

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4
Q

What is Wallerian Degeneration?

A

degen of axon/myelin below injury, mopped up by Macrophages

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5
Q

3 weeks post injury to PNS what do you get?

A

schwann cells proliferate, compact cord

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6
Q

How fast do PNS axons regrow?

A

0.5-3mm/day

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7
Q

how long for successful regen in PNS since initial injury?

A

~3months

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8
Q

How does the regenned PNS nerve look compared to normal?

A

thinner sheath

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9
Q

what happens if you get unsuccessful PNS regen?

A

neuroma formation

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10
Q

Repair in PNS is faster when?

A

crushed vs. cut

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11
Q

main therapeutic approach to PNS injury?

A

microsurgery

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12
Q

oligodendrocytes and CNS regen do what?

A

inhibit regrowth

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13
Q

secondary damage minutes to hours in SCI include 5 things:

A
  1. ischemia
  2. Ca2+ influx
  3. lipid peroxidation/free radicals
  4. glutamate excitotoxicity
  5. BBB break down
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14
Q

Treatment for SCI degenerative insults?

A

erythropoietin

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15
Q

Hours to days/weeks what happens in SCI? what happens? 3 things?

A

immune cells infiltrate
microglia activate
cytokines/chemokines released

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16
Q

what is a syrinx?

A

cavity formation for meningeal fibroblasts in SCI

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17
Q

What in the injury environment inhibits CNS regen? 2 big things things

A

astrocytic gliosis

Glial scar

18
Q

4 things needed to repair CNS?

A
  1. Neuroprotection
  2. Axononal regen/functional integration
  3. modulate astrocytic gliosis
  4. neural stem cells
19
Q

2 approaches to neural stem cells are?

A
  1. mobilise endogenous cells

2. transplant exogenous cells

20
Q

Another reason for lack of CNS regen besides injury environment?

A

lack of trophic support

no growth promoting factors

21
Q

what is sprouting?

A

an adjacent nerve grows new processes to take over injured nerve’s functions

22
Q

Astrocytic gliosis does what?

A

increase GFAP
cytokines
extracelular matrix, proteogylcans
becomes glial scar = barrier to regen

23
Q

research to prevent Astrocytic gliosis?

A

blocking extracellular matrix

24
Q

what happens if you knock out astrocytes completely in an SCI?

A

no regen at all

25
approach for Astrocytic gliosis?
regulation | block inhibitors secreted by astrocytes
26
What is Nogo? treatments?
Myelin inhibitor | testing anti-Nogo
27
What are axon guidance molecules?
promote, repel or guid regrowing axons
28
What does Nogo receptors activate?
Rho signalling = inhibits axon regrowth
29
What are Eph/Ephrins?
possible axon guidance molecules
30
What does Rho kinase in SCIs do?
activates astrocytes inhibiting regrowth
31
CNA vs. PNS degen?
CNS: slow PNS: quick
32
CNA vs. PNS nerve structure after injury?
CNS: destroyed PNS: intact
33
Schwann cells do what to injured PNS?
supports axon regrowth
34
What are the two main regions of neural stem cells?
1. subventricular zone (lateral ventricle) | 2. subgranular zone (hippocampus)
35
Problems with endogenous neural stem cells in SCIs? 4:
1. Proliferation 2. migration (blocked by inflamm/gliosis 3. differentiation 4. Survival
36
what are iPSC and ESC?
induced pluripotent stem cell | embryonic stem cell
37
what kind of therapy is likely for SCI Rx?
combination
38
How to help with functional regen?
physical therapy
39
3 myelin proteins are? what do they do?
Nogo MAG: myelin-associated glycoprotein OMcp: oligodendrocyte myelin glycoprotein bind to NogoR = inhibit regen
40
name 4 kinds of upregulated axon guidance molecules:
1. semaphorins 2. tenascin 3. cell adhesion molecules (N-CAM, L1, N-Cadherin) 4. EphA4/ephrinA5