CNS repair and regeneration Flashcards
What is SCI? Where is the body effected? What determines severity?
Spinal cord injury
sensory motor and autonomic control may be lost below the level that is damaged
higher up the injury on the spinal cord the larger the area affected
What is TBI? Who is it more common in
Traumatic brain injury
mainly young people more common in men than women
very common 445 head injuries every day
What determine the functional consequences of injury in the CNS
The size and site of injury not the type of injury
Why is CNS repair so complicated
Neurones terminally differentiated cells therefore cannot autorenew
Form complex maps of synapses and junctions therefore removal of one can lead to whole map disruption
What are some example of head injury?
Skull fractures
Cerebral haemorrhages
Aneurysms swelling of blood vessels increase intra cranial pressure and prone to haemorrhage
lacunar infarct (small localised effect over time dementia)
Axonal shearing due to impact
What is hypoxic injury?
Brain relies on glucose form blood to survive cells have no energy stores
if there is haemorrhage the demand quickly outstrips supply leading to an energy crisis in the brain which results in neuronal cell death
May also cause seizures that lead to further constriction of blood vessels and hypoxia of the brain
What is the response to injury
Neuronal death
Glial cells up regulate inflammatory mediators entangle gliosis and destruction of damaged neurones
Astrocytes try to seal the compromised BBB to prevent further oedema
Formation of glial scars that try to main integrity of CNS tissue
Why is there very little regrowth and repair in CNS tissue
Oligodendrocytes do not form guidance path for sprouting axons and instead produce inhibitory molecules Nogo and mag that inhibit neuronal repair continue to extras myelin proteins that lead to more debris
Astrocytes:
release factors to promote glial scar formation and release inhibitory proteoglycans that further prevent neuronal growth
Myelin debris is not cleaned up by macrophages like it is in the PNS
What is significant about CNS axons despite the inhibitory environment post trauma
They do have the intrinsic capacity for repair and new axonal growth and repair
What is the surgical treatment needed following TBI?
Decompressive emergency surgery to remove haematoma
What is rehabilitation when is it needed, how and what does it result in?
Aggressive neruorehabillitation needed ASAP
Can cause some functional recovery due to intrinsic capacity of neurones to want to grow and heal and the neuroplasticity of the brain and dendrites in reconnecting neurones into the communication networks
return on functioning depends on the quality intensity and motivation to carry of neruorehabillitation
increase neuroplasticity and what increases neuroplasticity ?
Modification of synaptic connections
Stimulated by neurotropic synthesis and release that leads to changes in synaptic morphology, membrane excitability, and neurotransmission.
Neurotrophic synthesis sand release best enhanced by neuronal activity hence the needed for aggressive neruorehabllition to activate neurones and maintain theory activity
What are some experimental treatment options for CNS regeneration and repair?
Trophic facotr therapy to increases neruonal regrowth
Inhibition of inhibitory molecules e.g. Nogo blockers
Endogenous stem cell therapy trying to stimulate migration and neruogenisis of stem cells located int he subventricualr zone
