W20-L3: Neural Regeneration Flashcards
When centrals axons or neurones are damage what happens?
- 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
What is the difference between CNS and PNS that allows the PNS to regenerate?
– Structure
– Cell types
– Molecules and guidance/repellent cues
In the PNS, up to 2 weeks post injury you will see
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
In the PNS, 3 weeks post injury you will see
• Schwann cells proliferate, forming a compact cord
• Growing axons penetrate the Schwann cell cord
–grow at 0.5-3mm/day
-muscle fibre atrophy
At around 3 months post injury in the PNS there will be
- Successful Regeneration
* Electrical activity restored causes Muscle fibre regeneration
What occurs when there is unsuccessful regeneration in the PNS?
Neuroma formation
Is repair quicker if peripheral nerves are crushed or cut?
Crushed, because the more precise the alignment the better the recovery (distal segment is continuous)
What occurs during the primary injury in the CNS?
Physical damage causes cell loss
What is treatment to combat primary injury?
tPA, decompression for spinal cord injury
In minutes to hours after damage to the CNS what do you see?
Secondary injury called Degenerative insults:
• Ischaemia
• Ca2+ influx
• lipid peroxidation & free radical production
• glutamate excitotoxicity
• BBB breakdown
In hours to days/weeks after damage to the CNS what do you see?
Secondary injury still and you will see:
• immune cell infiltration/microglial activation
• cytokines, chemokines, metalloproteases
What is the treatment to combat secondary injury occurring minutes to hours after insult?
EPO, methlyprenisolone (not is Aus)
In the days/weeks after damage to the CNS what do you see?
- axonal degeneration
- demyelination
- apoptosis
- astrocytic gliosis & glial scar
- also syrinx (cavity) formation, meningeal fibroblast migration
What treatments are there for secondary injury that occurs days/weeks after injury?
None
What will it take to effectively repair the CNS?
- Neuroprotection
- Axonal regeneration and functional integration
- Modulate astrocytic gliosis
- Neural stem cells
What stops axonal regeneration in the CNS?
Lack of trophic support and axon regrowth is inhibited by the injury environment
Axonal plasticity (sprouting) versus regeneration
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
Astrocytic gliosis
causes Glial Scar Formation that forms a barrier between undamaged tissue and injury site
What happens when you prevent astrocytic gliosis?
increased tissue destruction and degeneration, increased inflammation, inhibited BBB repair
What are Myelin inhibitors?
Inhibitory molecules in the injury environment bind to receptors on (re)growing axons/dendrites (neurites), binds to myelin debris eg Nogo
What are Axon Guidance Molecules?
Molecules that Promote, repel or guide growing axons. Many upregulated or re-expressed after injury in the adult eg. EphA4
How can we use stem cells to repair the nervous system after injury or disease?
- Transplant stem cells/neurons grown in tissue culture
* Use drugs to “activate” stem cells already present in the adult nervous system
Where are the Two main neurogenic regions in the adult mammalian brain?
- The subventricular zone (SVZ) of the lateral ventricle
- The subgranular zone (SGZ) of the dentate gyrus in the hippocampus
