W20/L3: Neural regeneration Flashcards

1
Q

Can neurons in the PNS regenerate/repair?

A

Yes - although repaid is often only partial

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2
Q

What are some cytological characteristics of a normal neuron?

A

Central nucleus

Dense Nissl substance

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3
Q

What is Nissl substance?

A

Ribosomes in the cell body, actively translating RNA

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4
Q

What changes initially happen in the neuron following PNS injury?

A

Nucleus becomes peripheral
Chromolysis
Wallerian degeneration

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5
Q

What is chromolysis?

A

aka chromatolysis = the loss of Nissl substance

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6
Q

What does Wallerian degeneration refer to?

A

The process of axon and myelin sheath degeneration below the site of injury

The debris is p’cytosed by m’phages.

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7
Q

At approximately what time point do reparative changes appear in a damaged PMS neuron?

A

3 weeks post-injury

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8
Q

What actions are taking place in the repair process of an injured PNS neuron?

A

Nucleus returns to central location
Nissl starts forming
Schwann cells proliferate forming a protective guide for the growing axon

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9
Q

About how long does it take for an injured PNS neuron to successfully regenerate?

A

3 months

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10
Q

Is a regenerated PNS axon completely normal?

A

No - it’s often a bit abnormal, for example the myelin sheath remains quite thin

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11
Q

What is a Neuroma?

A

A bungle of axon sprouts generated in PSN neural repair, which have no successfully made their way into the Schwann cell guide

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12
Q

What can a neuroma cause?

A

Painful / unwanted symptoms

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13
Q

What is a key predictor in successful PNS regeneration?

A

Precise alignment between the proximal and distal segments

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14
Q

What strategies can we use to increase possibility of successful regeneration via alignment?

A

Microsurgery to reattach proximal and distal stumps

Microsurgery with a nerve graft.

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15
Q

What are the myelinating cells of the PNS

A

Schwann cells

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16
Q

What are the myelinating cells of the CNS?

A

Oligodendrocytes

17
Q

Schwann cells vs oligodendrocytes: which ones are supportive to cell regeneration?

A

Schwann cells

18
Q

What does the primary injury refer to in CNS injuries?

A

The actual physical damage (compression/laceration)

19
Q

How can we minimise primary injury?

A

In many cases we can’t, but;

tPA in stroke & decompression in SCI

20
Q

Do interventions that minimise primary injury help with regeneration?

A

No - they just mitigate the amount of cellular damage

21
Q

What does secondary injury refer to?

A

The degenerative insults that take minutes to hours to cause damage

22
Q

Does secondary injury only happen in the exact location of the primary injury?

A

No - it can spread over a much larger site

23
Q

What sort of things cause secondary injury?

A
Ischaemia
Ca2+ influx
Lipid peroxidation & free radical prod.
Glutamate excitotoxicity
BBB breakdown
24
Q

What therapies exist to minimise secondary injury?

A

Methylprednisolone is used overseas
EPO is in clinical trials

Most therapies have failed though

25
What happens in the hours to days/weeks following CNS injury?
Infiltration of immune cells from periphery Activation/migration of microglial cells Resulting in cytokines, chemokines, and metalloproteases being released in the area
26
Eventually - days/weeks after CSN injury we have a lesions demonstrating:
``` Axonal degeneration Demyelination of remaining axons Apoptosis of neurons Astrocytic gliosis & glial scar Syrinx formation Meningeal fibroblast migration ```
27
What is a syrinx?
A fluid-filled cavity formed (in SCI) from the dilation of the central canal
28
What (4) steps would have to happen for effective CNS repair?
Neuroprotection (of surviving cells) Axonal & functional regeneration Modulate astrocytic gliosis Neural stem cells to replace lost cells
29
What 2 things can inhibit axonal regeneration?
Lack of trophic support | The injury environment blocking growth
30
What intervention can we use to provide trophic support?
Provide growth promoting factors | eg neurotrophins: NGF, BDNF
31
Why haven't the neurotrophins been implemented clinically?
They caused neuropathic pain in clincal trials
32
What intervention can we use to help axons regrow despite the injury environment?
Inhibit growth blocking factors
33
What are some of the factors that can block axonal regrowth?
Astrocytic gliosis/glial scar Myelin inhibitors Developmental guidance molecules
34
What's the difference between axonal sprouting and axonal regeneration
Axonal sprouting (aka plasticity) is when a surviving neuron sprouts extra synapses to take over the role of the lost neuron Axonal regeneration is when the damaged neuron regrows.