W20/L3: Neural regeneration Flashcards
Can neurons in the PNS regenerate/repair?
Yes - although repaid is often only partial
What are some cytological characteristics of a normal neuron?
Central nucleus
Dense Nissl substance
What is Nissl substance?
Ribosomes in the cell body, actively translating RNA
What changes initially happen in the neuron following PNS injury?
Nucleus becomes peripheral
Chromolysis
Wallerian degeneration
What is chromolysis?
aka chromatolysis = the loss of Nissl substance
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.
At approximately what time point do reparative changes appear in a damaged PMS neuron?
3 weeks post-injury
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
About how long does it take for an injured PNS neuron to successfully regenerate?
3 months
Is a regenerated PNS axon completely normal?
No - it’s often a bit abnormal, for example the myelin sheath remains quite thin
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
What can a neuroma cause?
Painful / unwanted symptoms
What is a key predictor in successful PNS regeneration?
Precise alignment between the proximal and distal segments
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.
What are the myelinating cells of the PNS
Schwann cells
What are the myelinating cells of the CNS?
Oligodendrocytes
Schwann cells vs oligodendrocytes: which ones are supportive to cell regeneration?
Schwann cells
What does the primary injury refer to in CNS injuries?
The actual physical damage (compression/laceration)
How can we minimise primary injury?
In many cases we can’t, but;
tPA in stroke & decompression in SCI
Do interventions that minimise primary injury help with regeneration?
No - they just mitigate the amount of cellular damage
What does secondary injury refer to?
The degenerative insults that take minutes to hours to cause damage
Does secondary injury only happen in the exact location of the primary injury?
No - it can spread over a much larger site
What sort of things cause secondary injury?
Ischaemia Ca2+ influx Lipid peroxidation & free radical prod. Glutamate excitotoxicity BBB breakdown
What therapies exist to minimise secondary injury?
Methylprednisolone is used overseas
EPO is in clinical trials
Most therapies have failed though
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
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
What is a syrinx?
A fluid-filled cavity formed (in SCI) from the dilation of the central canal
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
What 2 things can inhibit axonal regeneration?
Lack of trophic support
The injury environment blocking growth
What intervention can we use to provide trophic support?
Provide growth promoting factors
eg neurotrophins: NGF, BDNF
Why haven’t the neurotrophins been implemented clinically?
They caused neuropathic pain in clincal trials
What intervention can we use to help axons regrow despite the injury environment?
Inhibit growth blocking factors
What are some of the factors that can block axonal regrowth?
Astrocytic gliosis/glial scar
Myelin inhibitors
Developmental guidance molecules
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.
