Brain and Spinal Cord Repair (Dr Dixon) Flashcards
How does a CNS injury progress? (example of a spinal cord injury)?
- Local swelling at the site of the injury which pinches off blood perfusion and leads to ischaemia.
- Excessive release of glutamate and excitotoxicity of neurons and oligodendrocytes at the site of injury (scar tissue)
- Infiltration by immune cells (microglia and neutrophils)
- Free radical toxicity
- Apoptosis / necrosis
How do astrocytes help the body to reconstruct after damage?
Astrocytes begin production and secretion of cytokines, which ‘reactivates’ their proliferation. They infiltrate the legion and form a scar.
They express a complicated milieu of proteoglycans (chondroitin sulfate proteoglycans) at the scar boundary.
What do damaged axons in the CNS do in response to damage?
Retraction of released growth cone
Axons are demyelinated and degenerate or remain ‘fixed’ in the same place for years.
Does damage repair happen in the peripheral nervous system?
No, only occurs in the CNS
Reactive astrocytes and oligodendrocyte myelin-associated inhibitors (Nogo, MAG, chondroitin sulfate polyglycans). (not in PNS)
What are the symptoms of a spinal injury?
Involuntary muscle spasms
Loss of voluntary movement, sensation, balance
Poor or lost control of breathing, autonomic function (BP), bladder, sexual, bladder control)
What are the symptoms caused by in spinal injury?
Destruction of long ascending or descending spinal pathways.
To be repaired, axons must regrow and synaptic circuits must be re-established.
What kind of axons can be used for regeneration?
<10% of axons is enough to facilitate regrowth; they must be myelinated
What happens in an injury is the cell body is damaged?
The neuron is lost; there is no cell division in the adult brain to replace the lost neuron.
What happens if the axon is severed a significant distance away from the soma (cell body)?
There is a good chance of regeneration, primarily in the PNS
CNS neurons have the capacity to regenerate
What are some of the highlights in Neural Regeneration?
Rehabilitation of disabilities with exercise
Anti-inflammatory steroid - methylprednisone could be employed to minimise cell death and tissue damage if administered early enough after injury.
What can be done about CNS damage?
- Fix what we have; prevent cell death, promote axon regrowth, remove blockades
- Build around it; brain-machine interfaces that can interpret neural codes and output activity to periphery (organic or machine).
How does decompression and stabilisation of the spine help injury?
Anterior and posterior plates
Titanium cage verterbral repair
Delayed compression restores function even years after injury.
How does peripheral nerve bridging help injury?
Implanting avulsed roots or nerves into the spinal cord for muscle reinnervation and reducing neuropathic pain
What drugs can be used to promote CNS regeneration?
Inhibiting axon regeneration blockers in CNS myelin
Removing barriers formed by glial scars
Stimulating regrowth by signalling pathways
Replacement neurons damaged during injury with pluripotent embryonic stem cells
Engineering brain-machine interfaces to produce enhanced sensory feedback
What is the difference between the PNS and CNS environments?
Peripheral nerves regenerate at later stages to CNS nerves and the axons re-extend for the length they were damaged but stop before they reach the CNS.
This shows that the CNS environment is not conducive to regeneration of axons.
What cells are involved in myelination formation? In the CNS and PNS?
Oligodendrocytes in CNS
Schwann cells in PNS
Oligodendrocytes are inhibitory to axon regrowth in adult CNS regeneration
Scwann cells are supportive, as a growth surface and releasor of growth factors in PNS.
What is the role of astroglia?
In development; supports axon growth and cell migration
When mature; important for ion flux, synaptic function, BBB
In injury; accumulate in scar, release excess matrix; inhibit axon growth?
What are microglia and macrophages?
Microglia are resting
Macrophages are active
Both cells of the immune system, similar to monocytes
How does the neuron react to injury IMMEDIATELY?
Synaptic transmission immediately turned off
Cut ends pull apart and are sealed up. They swell sue to axonal transport in both directions.
How does the neuron react to injury WITHIN HOURS?
Synaptic terminal degenerates; accumulation of neurofilaments and vesicles
Astroglia surround the terminal normally; after axotomy,, astroglia interpose between terminal and target and caise terminal to be pulled away from post synaptic cell.
How does the neuron react to injury AFTER DAYS / WEEKS?
Myelin breaks up and leaves debris
Axon undergoes Wallerian degeneration
Chromatolysis - cell body swells; nissl and nucleus eccentric
