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Flashcards in Neural regeneration Deck (33):
1

What is the major difference between the CNS and the PNS in terms of regeneration?

PNS will regenerate, CNS will not

2

When damage occurs to a peripheral nerve, which portion of the nerve can regenerate? In which direction?

Proximal portion of the axon can regenerate distally

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3

Is neuronal repair in the PNS full or partial?

Can be full, but is often partial

4

If a peripheral nerve's cell body is in the CNS, can it still undergo regeneration?

If the axon is damaged in the periphery, the proximal axon can regenerate distally

5

What happens when neuronal injury occurs in the CNS?

Some neurons die

Some neurons retract processes but can sprout

Glial scars inhibit regrowth

 

6

What determines the extent of neuronal repair in the CNS (ie. whether full or partial repair occurs)?

Severity of neuronal injury

Location of injury

7

What are the three broad differences between the CNS and the PNS that allows the PNS to regenerate, but not the CNS?

NS structure

Cell types present

Molecules and guidance/repellent cues

8

Describe the changes that occur in peripheral nerves after injury?

2 weeks post-injury: nucleus moves to the periphery, loss of Nissl substance, Wallerian degeneration, muscle fibre atrophy

3 weeks post injury: Schwann cells proliferate, nucleus moves centrally, growing axons penetrate Schwann cell cord, muscle fibre atrophy

3 months post injury: successful regeneration, muscle fibre regeneration

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9

What is Wallerian degeneration?

Degeneration of axon and myelin sheath below the site of injury

10

What happens to a neuron if it does not regenerate successfully?

Neuroma formation 

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11

Why might unsuccessful regeneration occur and result in neuroma formation?

Growing axon cannot find right target

12

Is repair faster if the neuron is cut or crushed? Why?

Faster when crushed, because the Schwann cells and ECM (which act as a guide) remain continuous

More precise alignment allows better recovery and regeneration

13

What is the main therapeutic approach to PNS injury?

Microsurgery to reattach proximal and distal stumps or a nerve graft

14

Decsribe the primary injury that occurs in CNS neural injury?

PRIMARY INJURY

Immediate: Physical damage - cell loss

 

15

Describe the secondary injuries that occur in CNS neural injury?

SECONDARY INJURY

Minutes to hours: ischaemia, Ca influx, lipid peroxidation and free radical production, glutamate excitotoxicity, BBB breakdown

Hours to days/weeks: immune cell infiltration, microglial activation, cytokines, chemokines, metalloproteases

Days/weeks: axonal degeneration, demyelination, apoptosis, astrocytic gliosis and glial scar, cavity formation

 

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16

What must be achieved in order to effectively repair the CNS?

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17

What broad features inhibit axonal regrowth?

Lack of trophic support

Injury environment inhibiting growth

18

How can a lack of trophic support be combatted in order to support axonal regeneration?

Provide growth promoting factors eg. neurotrophins

19

How can the injury environment be altered so that it does not inihibit axonal growth?

Inhibit growth blocking factors: astrocytic gliosis and glial scar, myelin inhibitors, developmental guidance molecules

20

Describe the difference between axonal plasticity and axonal regeneration?

Plasticity: axons sprout; those near the injured neuron grow extra processes

Regeneration: neuron that was damaged grows a new axon

21

Describe astrocytic gliosis?

Astrocytes become hypertrophic, proliferate, interdigitate processes, secrete cytokines and growth factors, secrete ECM, upregulate axon guidance molecules

This all leads to glial scar formation

22

Why can astrocytic gliosis be inhibitory to neuronal regeneration?

Glial scar forms a barrier between undamaged tissue and and injury site 

23

Which techniques targetting astrocytic gliosis have resulted in increased neuronal regeneration?

Blocking of astrocyte ECM

GFAP/Vimentin double knockout

Astrocyte ablation 

24

Which molecules in the injury environment inhibit axon regrowth?

Myelin inhibitors on myelin debris

Guidance molecules on actiavted astrocytes

25

Which particular myelin proteins are inhibitory in the injury environment, and why are they inhibitory?

Nogo, MAG and OMgp

All bind to Nogo receptor, which activates the Rho signalling pathway > inhibits axon growth

26

How are myelin proteins being targetted to encourage axonal regrowth?

Gene knockouts, Nogo blockers (Anti-Nogo antibody) and Rho inhibitors

27

What are axon guidance molecules?

Molecules that promote, repel or guide growing axons

28

Describe why Rho activation inhibits axonal growth?

Causes growth cone to shrink

Activates astrocytes 

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29

Compare and contrast the CNS and PNS injury environments?

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30

Describe two strategies for using stem cells to repair the nervous system?

1. Transplant stem cells/neurons

2. Use drugs to activate stem cells already present in NS

31

What are the two main neurogenic regions in the brain?

Subventricular zone

Subgranular zone 

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32

Why don't endogenous neural stem cells nromally effectively repair the CNS?

Cells must proliferate, migrate, differentiate, and then survive

33

What is the most important non-pharmacological form of therapy for functional regeneration?

Physical therapy and muscle/neuronal activity