Regeneration in the NS Flashcards
Why is regeneration in the NS important?
Large number of traumatic injuries in peripheral nerves annually
What are some causes of peripheral nerve damage?
- Spinal cord injury
- Stroke
- Degenerative diseases
- Road accidents
What is the regenerative capacity of lower animals (reptiles, amphibians, fish)?
Huge
How is xenopus tadpole tail regeneration triggered?
By BMPs
What is the ‘critical period’ of regeneration in the tadpole?
Time after this, there is a loss of BMP expression and the trail cannot regenerate
In lower animals, what is regeneration dependant on?
What are exceptions to this?
Nerves
Worms - if cut in half, both ends grow back
What is a blastema?
What is in close proximity to it? What does this allow?
Pluripotent stem cells in a salamander
In close proximity to nerves - where Schwann cells migrate in from and allow regrowth
In a nerve, what do the insulating layers impact on?
The damage the nerve can get and the ability of the nerve to repair itself
Who classified nerve injuries?
Seddon
What is Neuropraxia?
Damage to some of the insulating layers of the nerve - produced by compression or stretching
What does neuropraxia affect?
Conduction of the nerve (because of damage to the insulating layers)
What is axonotmesis?
Division of the nerve but the connective tissue remains intact
Nerve is resected
What is neuromesis?
Division through the entire nerve (through insulating layers and through the axon)
How was Seddons classification of nerves expanded?
At the level of axontemeis and neuromesis, can have different stages of conduction - some preservation or complete loss
What happens if the injury happens close to the cell body? (In the PNS)
Get cell death
What happens if the injury is not close to the cell body?
In the PNS
Re-organisation and re-expression of immature features (tubulin), depending upon the level of damage
What is Wallerian degeneration?
In the PNS:
When the nerve is damaged, the distal part of it starts to degrade as macrophages invade the area and break up the remnants of the destroyed cells and myelin to clean the area
What happens to muscle when the nerve innervating it is damaged? (PNS)
- Muscle atrophy
- AChR reversal to embryonic (de-differentiation)
- MUSK receptor increase
In denervated muscle, what can external electrical input help? (PNS)
Prevent atrophy and degeneration
How is the distal part of the nerve regenerated, if the connective tissue remains intact?
(PNS)
- Mitosis of Schwann cells, which supply growth factors
- Schwann cells rearrange themselves to produce BANDS OF BUNGNER (rows)
- This provides a scaffold for new axon fibres through the new connective tissue
What is sprouting?
When does it occur?
Compensation of loss of innervation to a muscle by an adjacent nerve innervating it instead
Occurs when peripheral nerves are damaged
What injury to the nerves have the biggest impact and why?
How can this be artificially compensated?
Injuries when the nerve is cut
As this disrupts the basal lamina and extracellular matrix
Schwann cells cannot grow
Artificially compensated by joining the 2 stumps of the neuron together
OR
By making a scaffold to breach the 2 sides
What occurs in the spinal cord after axon injury?
- Inefficient sprouting
- Followed by failed regeneration and degeneration
- Cysts and glial scar formation
- Poor recovery of connections
Why is regeneration in the spinal cord poor?
Inhibitory myelin and incorrect glia
What happens if take neurons from the CNS and expose it to Schwann cells from the periphery?
Axon will grow
What happens if expose a CNS neurons to an olligodendrocyte in vitro?
Axons will avoid the olligodenrocyte
What is the difference between olligodendrocytes and Schwann cells?
Olligo - myelinate in the CNS
Schwann - myelinate in the PNS
What happens if make antibodies against myelin in the CNS (autoimmunisation)?
What does this suggest?
Increases regeneration
Suggests there is a protein in myelin in the CNS which inhibits growth
What is nogo-a?
Protein in oligos and developing neurons in the CNS which inhibits axon growth
What organisms dont have nogo-a?
Fish and salamanders, which can regenerate
How does nogo-a work?
In the CNS:
Present in the oligo membrane - interacts with nogo receptors in the membrane and with the P75 in the neuron
Blocks the signalling pathway
What does anti-nogo do?
Improves regeneration in the spinal cord and facilitates rerouting
Why is there an objection to nogo inhibiting neuron regeneration? (4 things)
- No correlation between nogo/receptor level and regenerative capacity
- Transplanted hippocampal neurons grow axons into myelin (not inhibited)
- Much myelin is removed by macrophages after damage and regeneration is still porr
- Regeneration is poor in grey matter (where there is no myelin)
How to glial scars prevent regeneration?
Contains astrocytes, which are inhibitors of axonal growth
How do cysts prevent regeneration?
Contain inhibitory matrix, which axons cannot find their way through
Secretion of inhibitory CSPGs
How can spinal cord bridges overcome damage in the CNS?
What are they filled with to help achieve this?
Structure by-pass glial scars, to guide axons through a different route to their target
Filled with GFs ECM and synthetic matrix
What can foetal cells be used for?
- Treat Parkinsons and Huntingtons
What happens to the fish and amphibia retina through life?
Keep growing, retinal stem cells add to the retina over time
What happens in the mammalian forebrain SVZ and dentate gyrus?
Slow, but continuous formation of new neurons
What are olfactory ensheating cells and what can they do?
Wrap olfactory axon bundles in the olfactory bulb
Have the ability to make new neurons in vitro
