Neural Regeneration Flashcards Preview

MD1 Neuroscience > Neural Regeneration > Flashcards

Flashcards in Neural Regeneration Deck (51):
1

What are the peripheral and central projections?

Central > central
Central > peripheral
Peripheral > peripheral

2

Which projections are together in peripheral nerves?

Central > peripheral
Peripheral > peripheral

3

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

Proximal part regenerates distally

4

What is the totality of peripheral nerve repair?

Can be full but often partial

5

What happens when central axons/neurons are damaged?

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

6

What does a normal neuron's cell body have?

Central nucleus
Dense Nissl substance

7

What happens to the neuron two weeks post-injury?

Peripheral nucleus
Chromatolysis
Wallerian degeneration
Muscle fibre atrophy

8

What happens in Wallerian degeneration?

Degeneration of axon and myelin sheath below site of injury
Debris phagocytosed by macrophages - migrate from peripheral immune system

9

What is chromatolysis

Nissl substance almost gone
What's left has moved to edges of cell body

10

What happens to the neuron three weeks post-injury?

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

11

What happens to the neuron three months post-injury?

Successful regeneration
Electrical activity restored
Muscle fibre regeneration

12

What happens with unsuccessful regeneration?

Neuroma formation

13

What happens in neuroma formation?

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

14

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

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

15

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

No, it's faster when an axon is crushed

16

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

In a crush injury, the guide is continuous

17

What is the main therapeutic approach to PNS injury?

Microsurgery
Reattach proximal and distal stumps or insert nerve graft

18

Describe the sequence of events in a crush injury

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

19

Describe the sequence of events in a cut injury

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

20

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

Physical damage
Cell loss

21

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

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

22

What happens in the minutes to hours after CNS injury?

Degenerative insults
- Ischaemia
- Ca influx
- Lipid peroxidation and free radical production
- Glutamate excitotoxicity
- BBB breakdown

23

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

Erythropoietin (Epo) in clinical trials
Active area of research

24

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

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

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