W20-L3: Neural Regeneration

Question 1

When centrals axons or neurones are damage what happens?

Answer 1

• Some neurons die
• Some neurons retract processes but can “sprout” and make new local connections
• normally little or no real regeneration as glial scar inhibits regrowth

Question 2

What is the difference between CNS and PNS that allows the PNS to regenerate?

Answer 2

– Structure
– Cell types
– Molecules and guidance/repellent cues

Question 3

In the PNS, up to 2 weeks post injury you will see

Answer 3

Peripheral nucleus, loss of Nissl substance and wallerian degeneration (degeneration of axon and myelin sheath below site of injury, debris is phagocytosed) and muscle fibre atrophy

Question 4

In the PNS, 3 weeks post injury you will see

Answer 4

• Schwann cells proliferate, forming a compact cord
• Growing axons penetrate the Schwann cell cord
–grow at 0.5-3mm/day
-muscle fibre atrophy

Question 5

At around 3 months post injury in the PNS there will be

Answer 5

• Successful Regeneration

* Electrical activity restored causes Muscle fibre regeneration

Question 6

What occurs when there is unsuccessful regeneration in the PNS?

Answer 6

Neuroma formation

Question 7

Is repair quicker if peripheral nerves are crushed or cut?

Answer 7

Crushed, because the more precise the alignment the better the recovery (distal segment is continuous)

Question 8

What occurs during the primary injury in the CNS?

Answer 8

Physical damage causes cell loss

Question 9

What is treatment to combat primary injury?

Answer 9

tPA, decompression for spinal cord injury

Question 10

In minutes to hours after damage to the CNS what do you see?

Answer 10

Secondary injury called Degenerative insults:
• Ischaemia
• Ca2+ influx
• lipid peroxidation & free radical production
• glutamate excitotoxicity
• BBB breakdown

Question 11

In hours to days/weeks after damage to the CNS what do you see?

Answer 11

Secondary injury still and you will see:
• immune cell infiltration/microglial activation
• cytokines, chemokines, metalloproteases

Question 12

What is the treatment to combat secondary injury occurring minutes to hours after insult?

Answer 12

EPO, methlyprenisolone (not is Aus)

Question 13

In the days/weeks after damage to the CNS what do you see?

Answer 13

• axonal degeneration
• demyelination
• apoptosis
• astrocytic gliosis & glial scar
• also syrinx (cavity) formation, meningeal fibroblast migration

Question 14

What treatments are there for secondary injury that occurs days/weeks after injury?

Answer 14

None

Question 15

What will it take to effectively repair the CNS?

Answer 15

• Neuroprotection
• Axonal regeneration and functional integration
• Modulate astrocytic gliosis
• Neural stem cells

Question 16

What stops axonal regeneration in the CNS?

Answer 16

Lack of trophic support and axon regrowth is inhibited by the injury environment

Question 17

Axonal plasticity (sprouting) versus regeneration

Answer 17

Axonal plasticity: nearby neurone spreads an axon to innervate the damaged axons structure, has to be close
Regeneration: New axon from the damaged neurone innervates structure

Question 18

Astrocytic gliosis

Answer 18

causes Glial Scar Formation that forms a barrier between undamaged tissue and injury site

Question 19

What happens when you prevent astrocytic gliosis?

Answer 19

increased tissue destruction and degeneration, increased inflammation, inhibited BBB repair

Question 20

What are Myelin inhibitors?

Answer 20

Inhibitory molecules in the injury environment bind to receptors on (re)growing axons/dendrites (neurites), binds to myelin debris eg Nogo

Question 21

What are Axon Guidance Molecules?

Answer 21

Molecules that Promote, repel or guide growing axons. Many upregulated or re-expressed after injury in the adult eg. EphA4

Question 22

How can we use stem cells to repair the nervous system after injury or disease?

Answer 22

• Transplant stem cells/neurons grown in tissue culture

* Use drugs to “activate” stem cells already present in the adult nervous system

Question 23

Where are the Two main neurogenic regions in the adult mammalian brain?

Answer 23

• The subventricular zone (SVZ) of the lateral ventricle

- The subgranular zone (SGZ) of the dentate gyrus in the hippocampus