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MD1 Neuroscience > Neural Regeneration > Flashcards

Neural Regeneration Flashcards

1
Q

What are the peripheral and central projections?

A

Central > central
Central > peripheral
Peripheral > peripheral

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2
Q

Which projections are together in peripheral nerves?

A

Central > peripheral

Peripheral > peripheral

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3
Q

Which part of the axon can regenerate when peripheral axons are damaged?

A

Proximal part regenerates distally

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4
Q

What is the totality of peripheral nerve repair?

A

Can be full but often partial

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5
Q

What happens when central axons/neurons are damaged?

A

Some neurons dies
Some neurons retract processes but can sprout and make new local connections
Normally little or no regeneration as glial scar inhibits regrowth

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6
Q

What does a normal neuron’s cell body have?

A

Central nucleus

Dense Nissl substance

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7
Q

What happens to the neuron two weeks post-injury?

A

Peripheral nucleus
Chromatolysis
Wallerian degeneration
Muscle fibre atrophy

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8
Q

What happens in Wallerian degeneration?

A

Degeneration of axon and myelin sheath below site of injury

Debris phagocytosed by macrophages - migrate from peripheral immune system

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9
Q

What is chromatolysis

A

Nissl substance almost gone

What’s left has moved to edges of cell body

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10
Q

What happens to the neuron three weeks post-injury?

A

Schwann cells proliferate, forming compact cord
Growing axons penetrate Schwann cell cord
Grow at 0.5-3 mm/day
Muscle fibre atrophy

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11
Q

What happens to the neuron three months post-injury?

A

Successful regeneration
Electrical activity restored
Muscle fibre regeneration

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12
Q

What happens with unsuccessful regeneration?

A

Neuroma formation

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13
Q

What happens in neuroma formation?

A

If regrowing axon can’t find where it has to go
Schwann cells still secreting growing signals
Neuron grows and grows without direction
Can be very painful since neuron is alive and signalling without a target

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14
Q

What are the molecular and cellular responses that promote peripheral nerve regeneration?

A

1) Injury to peripheral nerve
2)
- Neuron expresses growth-related genes
- Macrophages rapidly remove myelin debris
- Schwann cellrs release axon growth-promoting signals, neurotrophins, and ECM
3)
- Growth cone of axon senses environment and causes axon to grow
- Newly made myelin expresses adhesion molecules detected by growth cone
- Proliferating Schwann cells promote axon regeneration

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15
Q

Is repair fast when an axon is cut, rather than crushed?

A

No, it’s faster when an axon is crushed

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16
Q

What is the difference in the guide provided by Schwann cells and ECM in distal segments between when a nerve is crushed and cut?

A

In a crush injury, the guide is continuous

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17
Q

What is the main therapeutic approach to PNS injury?

A

Microsurgery

Reattach proximal and distal stumps or insert nerve graft

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18
Q

Describe the sequence of events in a crush injury

A 
Crush
Dieback
- Basal lamina intact
- Axons can't get lost along way
- Reach appropriate targets
Good regrowth
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19
Q

Describe the sequence of events in a cut injury

A 
Cut
Dieback
Variable growth
- Some find right target
- Some find wrong targets
- Some don't find targets at all
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20
Q

What are the immediate consequences of primary injury to the CNS?

A

Physical damage

Cell loss

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21
Q

What is the treatment for immediate consequences of primary injury to the CNS?

A

Minimise extent of primary damage
- Eg: tPA for stroke
Decompression in clinical trials

22
Q

What happens in the minutes to hours after CNS injury?

A

Degenerative insults

  • Ischaemia
  • Ca influx
  • Lipid peroxidation and free radical production
  • Glutamate excitotoxicity
  • BBB breakdown
23
Q

What is the treatment for the secondary injury that happens in the minutes to hours after CNS injury?

A

Erythropoietin (Epo) in clinical trials

Active area of research

24
Q

What happens in the hours to days/weeks after CNS injury?

A

Immune cell infiltration/microglial activation

Cytokines, chemokines and metalloproteases

25
What happens in the days/weeks after CNS injury?
Axonal degeneration demyelination Apoptosis - neuronal and oligodendroglial Astrocytic gliosis and glial scar Syrinx (cavity) formation and meningeal fibroblast migration
26
What is the treatment for the secondary injury that happens in the days/weeks after CNS injury?
None yet Many clinical trials Active area of research
27
What will it take to effectively repair the CNS?
``` Neuroprotection Axonal regeneration and functional integration - Regrowth of suriviving neurons - Remyelination Modulate astrocytic gliosis Neural stem cells - Replacement of lost cells - Mobilise endogenous cells - Transplant exogenous cells ```
28
What stops axonal regeneration?
Lack of trophic support | Axon regrowth inhibited by injury environment
29
What can be done to counteract lack of trophic support?
Provide growth promoting factors like neurotrophins
30
What can be done to counteract axon regrowth inhibition?
Inhibit growth blocking factors
31
Is axonal plasticity true axon regeneration?
No, since axons close by sprout new branches to innervate area that's lost it Don't get full repair
32
What happens in astrocytic gliosis?
Upregulate astrocyte cytoskeletal proteins Hypertrophic Proliferate Interdigitate processes Secrete cytokines and growth factors Secrete ECM Upregulate expression of developmental axon guidance molecules
33
What does astrocytic gliosis lead to?
Glial scar formation - forms barrier between undamaged tissue and injury site
34
What are the good aspects of astrocytic gliosis?
Wound sealing BBB repair Growth factors increase glutamate transporters
35
What are myelin inhibitors?
Inhibitory molecules in injury environment binding to receptors on regrowing axons/dendrites
36
Where are myelin inhibitors?
On myelin debris
37
Where are axon guidance molecules?
On activated astrocytes
38
What receptor do all myelin proteins bind to?
Nogo receptor
39
What does binding to the Nogo receptor activate?
Rho signalling pathway | Inhibits axon growth by retracting growth coneIn
40
What happens when animal models are given Nogo blockers?
Some regeneration
41
What happens when animal models are given Rho inhibitors?
Some regeneration
42
What are axon guidance molecules?
``` Promote, repel, or guide growing axons Many upregulated or re-expressed after injury - Semaphorins - Tenascin - Cell adhesion molecules - Ephrins ```
43
In terms of structure, why is the PNS permissive for regrowth and CNS is not?
PNS: relatively simple structure CNS: complex structure
44
In terms of degeneration of the distal axon, why is the PNS permissive for regrowth and CNS is not?
PNS: degeneration of distal axon and myelin fast CNS: degeneration of distal axon and myelin slow
45
In terms of myelinating cells, why is the PNS permissive for regrowth and CNS is not?
PNS: Schwann cell supports axon regrowth CNS: oligodendrocyte inhibits axon regrowth
46
In terms of nerve structure, why is the PNS permissive for regrowth and CNS is not?
PNS: nerve structure often remains largely intact and provides conduit for regrowth CNS: neural structure destroyed
47
In terms of phagocytosis, why is the PNS permissive for regrowth and CNS is not?
PNS: macrophages phagocytose debris CNS: macrophages phagocytose debris and enhance/diminish inflammatory response
48
In terms of cellular environment, why is the PNS permissive for regrowth and CNS is not?
PNS: Schwann cells and macrophages only cell types present CNS: complex cellular environment including - Neuronal cell bodies - Reactive astrocytes - Oligodendrocytes - Macrophages - Other inflammatory cells
49
What are the two main regions in the adult brain where neural stem cells live?
``` Subventricular zone (SVZ) of lateral ventricle Subgranular zone (SGZ) of dentate gyrus in hippocampus ```
50
Why don't endogenous neural stem cells normally effectively repair the nervous system?
Rarely become neurons - often become glial cells
51
Is monotherapy or a combination of therapies likely to be needed?
Combination of therapies

MD1 Neuroscience (55 decks)

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