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6. Neuro > W20/L3: Neural regeneration > Flashcards

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
Q

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

A

Infiltration of immune cells from periphery
Activation/migration of microglial cells

Resulting in cytokines, chemokines, and metalloproteases being released in the area

26
Q

Eventually - days/weeks after CSN injury we have a lesions demonstrating:

A 
Axonal degeneration
Demyelination of remaining axons
Apoptosis of neurons
Astrocytic gliosis & glial scar
Syrinx formation
Meningeal fibroblast migration
27
Q

What is a syrinx?

A

A fluid-filled cavity formed (in SCI) from the dilation of the central canal

28
Q

What (4) steps would have to happen for effective CNS repair?

A

Neuroprotection (of surviving cells)
Axonal & functional regeneration
Modulate astrocytic gliosis
Neural stem cells to replace lost cells

29
Q

What 2 things can inhibit axonal regeneration?

A

Lack of trophic support

The injury environment blocking growth

30
Q

What intervention can we use to provide trophic support?

A

Provide growth promoting factors

eg neurotrophins: NGF, BDNF

31
Q

Why haven’t the neurotrophins been implemented clinically?

A

They caused neuropathic pain in clincal trials

32
Q

What intervention can we use to help axons regrow despite the injury environment?

A

Inhibit growth blocking factors

33
Q

What are some of the factors that can block axonal regrowth?

A

Astrocytic gliosis/glial scar
Myelin inhibitors
Developmental guidance molecules

34
Q

What’s the difference between axonal sprouting and axonal regeneration

A

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.

6. Neuro (33 decks)

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