Brain and Spinal Cord Repair Flashcards
What are spinal cord injuries usually caused by? (19:55)
- 38.5%; car accidents
- 24.5%; violent encounters e.g. guns/knives
- Rest; sporting accidents, falls, work-related accidents
What is the demographic like for spinal cord injury?
- 55% of patients are between 16 and 30 years old
- > 80% of patients are male
What is the typical progression like of CNS injury WRT the spinal cord?
- Local swelling at the site of injury; punches off blood perfusion = ischaemia (secondary problem)
- Excessive release of Glu and excitotoxicity of neruons and oligodendrocytes at site of injury
- Infiltration by immune cells (microglia, neutrophils) = scar tissue (bad)
- Free radical (NOS etc.) toxicity
- Apoptosis/necrosis
Describe the restructuring that occurs in response to damage in the CNS?
- Astrocytes begin production and secretion of cytokines; ‘reactivates’ proliferation.
- Infiltrate the lesion and form a scar
- Astrocytes expresses a complex milieu of proteoglycans (chondroitin sulfate proteoglycans) at the scar boundary
- Damage to axons in the CNS results in retraction of resealed growth cone where it stalls indefinitely; scar tissue blocks axon regeneration
- Axons are demyelinated and degenerate, or remain ‘fixed’ in place for years.
Explain why the regeneration of axons and resulting functional recovering occurs in the peripheral nervous system, but not the CNS.
Two entities within the CNS are responsible for the CNS-specific hostile environment:
1) Reactive astrocytes
2) Oligodendrocyte myelin-associated inhibitors e.g. Nogo, MAG, OMgp, chondroitin sulfate proteoglycans
What are the symptoms of spinal cord injury?
- Involuntary muscle spasms
- Loss of:
• Voluntary movement
• Sensation
• Balance
• Control of breathing
• Autonomic functions (BP)
• Bladder
• Sexual
• Bowel control
What are the symptoms of spinal cord attributed to? What must occur to repair these pathways?
- Destruction of long ascending or descending spinal pathways
To repair:
- Axons must regrow
- Synaptic circuits must be re-established
What are the requirements for restoring function to CNS neurons? Methods?
- Transection of the cord is rare (complete tear)
- <10% axons can support substantial functional recovery
- Even ‘complete’ injuries recover some function
- Surviving axons need to be myelinated; scar tissue leads to progressive degeneration
> 4-aminopyridine improves conduction
> Stem and other cells remyelinate spinal axons - Reversing learned “non-use”
> Even a short period of non-use can turn off circuits
> Intensive “forced use” exercises required to restore function
What are the principles of neuron response to injury?
- If the cell body is damaged, the neuron dies and is not replaced by cell division in the adult, mature brain
- If the axon is damaged or severed at a distance from the soma (cell body), there is a good chance of regeneration (primarily in the PNS); the further away the better
- CNS neurons have the CAPACITY to regenerate
- Presynaptic and postsynaptic neurons are also affected and may degenerate; chain reaction downstream
Describe the historical treatment of CNS injury (1920s+).
- Development of X-ray technologies in 1920s allowed visualisation of spinal injuries and more accurate prognosis of outcomes
- By middle of 20th century, standard to stabilise injuries, fix them in place, rehabilitate disabilities w/exercise
- 1990s; anti-inflammatory steroid methylprednisolone used to minimise cell death and tissue damage, if administered early enough after injury
What are today’s principles regarding how to tackle CNS damage?
Fix what’s left:
- Prevent cell death
- Promote axon regrowth
- Remove blockages
Build around it:
- Brain-machine interfaces that interpret neural codes and output activity to periphery (organic or machine)
What surgical advances have been made WRT treating CNS damage?
Decompression and stabilisation of the spine:
- Anterior and posterior plates
- Titanium cage vertebral repair
- Delayed decompression restores function even years after injury
Urological procedures:
- Suprapubic catheterisation
- Mitrafanoff procedure; use of appendix to allow catheterising the bladder through belly button
- Vocare sacral stimulation
Syringomyelic cysts:
- Removing adhesions and untethering of the cord collapses syringomyelic cells with lower rate of recurrence
- Restoring CSF flow is key to preventing cyst development
Peripheral nerve bridging (most useful):
- Implanting avulsed roots or nerves into the spinal cord; bypassing injury site (muscle reinnervation, reduced neuropathic pain)
- Bridging nerves from above the injury site to organs below
How can drugs promote CNS regeneration?
- Inhibiting the axon regeneration blockers in CNS myelin
- Removing barriers formed by glia scars
- Stimulating regrowth by signalling pathways
- Replacement of neurons damaged during injury with embryonic stem cells
- Engineering brain-machine interfaces to produce enhanced sensory feedback prosthetics (bionic/cybernetics)
What is the timeline of understanding of Neural Regeneration?
- 1830s; First evidence of regeneration of severed sciatic nerve in rabbits
- 1890s; CNS nerves appear to attempt to regenerate but can’t; introduce ‘hostile CNS environment’ concept
- 1969; Neurons demonstrated to establish new synapses and reorganise networks after injury
- 1982; Crushed peripheral rat axons shown to grow in rat brain in the presence of its peripheral nerve graft, but stalls upon reaching the boundary of the CNS
What types of glial cells are there?
- Myelin-forming (Oligodendrocytes of CNS, Schwann cells of PNS)
- And astrocytes (non-myelin forming)
