W20/L3: Neural regeneration Flashcards Preview

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

Flashcards in W20/L3: Neural regeneration Deck (34):
1

Can neurons in the PNS regenerate/repair?

Yes - although repaid is often only partial

2

What are some cytological characteristics of a normal neuron?

Central nucleus
Dense Nissl substance

3

What is Nissl substance?

Ribosomes in the cell body, actively translating RNA

4

What changes initially happen in the neuron following PNS injury?

Nucleus becomes peripheral
Chromolysis
Wallerian degeneration

5

What is chromolysis?

aka chromatolysis = the loss of Nissl substance

6

What does Wallerian degeneration refer to?

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

The debris is p'cytosed by m'phages.

7

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

3 weeks post-injury

8

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

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

9

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

3 months

10

Is a regenerated PNS axon completely normal?

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

11

What is a Neuroma?

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

12

What can a neuroma cause?

Painful / unwanted symptoms

13

What is a key predictor in successful PNS regeneration?

Precise alignment between the proximal and distal segments

14

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

Microsurgery to reattach proximal and distal stumps

Microsurgery with a nerve graft.

15

What are the myelinating cells of the PNS

Schwann cells

16

What are the myelinating cells of the CNS?

Oligodendrocytes

17

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

Schwann cells

18

What does the primary injury refer to in CNS injuries?

The actual physical damage (compression/laceration)

19

How can we minimise primary injury?

In many cases we can't, but;

tPA in stroke & decompression in SCI

20

Do interventions that minimise primary injury help with regeneration?

No - they just mitigate the amount of cellular damage

21

What does secondary injury refer to?

The degenerative insults that take minutes to hours to cause damage

22

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

No - it can spread over a much larger site

23

What sort of things cause secondary injury?

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

24

What therapies exist to minimise secondary injury?

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.