Regeneration In CNS & PNS Flashcards
Current treatments for spinal cord injury
Spinal decompression
Neuro protection (steroid treatments, hypothermia - rare cases)
Rehabilitation (only certified treatment)
Assistive devices
Spinal decompression
After trauma, damage to spinal cord causes swelling
Surgical decompression of cord reduces the enlargement
Peripheral nerve regeneration
Stumps of growing axons
Central nerve regeneration
Do not regenerate - Die
Successful CNS regeneration - lamprey
Can fully regenerate its spinal cord after transection
Within 3 months- able to swim, burrow and flip around like normal
Repair and regeneration occurs after re transection
PNS vs CNS regeneration
Axon regeneration fails in CNS because of inhibitory environment and lack of regenerative ability of CNS axons
PNS axons regenerate because highly regenerative ability and permissive environment
PNS regeneration: cut vs crush
Cut: not as good as crush - larger task to accomplish
Crush: lesions regenerate better due to intact ECM. Acts as guidance channel for regrowth
Wallerian degeneration in PNS: conditions for successful regrowth
Schwann cells must be present and form bands of bungner
Lesion gap must also be vascularised and fibroblasts must for connective tissues
Grafts of extracellular matrix tubes into a cut nerve are insufficient to promote regeneration
Schwann cells needed
Recovery after PNS injury (crush) regeneration rate
Regeneration rates vary but usually around 1-1.5 mm/day in successful cases
PNS regeneration: importance of schwann cells and timing
Schwann cells in dense gated peripheral nerve only remain permissive for 2-3 months
Problem? Human rate of repair is very slow
Results? Proximal structures well innervated, distal structures poorly Innervate
Muscle end plates lose ability to become reinnervated after ~1yr
Muscles can become severely atrophied in absence of innervation
Using PNS environment within the CNS for repair
CNS injury
PNS nerve graft transplanted to create bridge for regrowing axons
Results - axons grew into the graft but not beyond (back into CNS)
Precondition lesions of the peripheral inside a robust regenerative response in CNS
Crushing the peripheral nerve enhances CNS regeneration within spinal cord of dorsal column axons
Upregulated series of genes (GAP 43)
High level of regeneration in sensory neurones
Have to do peripheral injury before CNS injury so not clinically relevant
Shown to work in optic nerve too but not motor axons
Intrinsic mechanisms to allow repair
Neuron cell survival
Axon elongation
Axon guidance to target
Appropriate target interaction and synapse formation
Activation of target in functionally meaningful way (functional repair)
Vascular supply
Regeneration (long distance?), replacement
Neuronal plasticity - nearby neurons take over the function of damaged neurons
Neuronal plasticity: developing nervous system
High potential for plasticity
Neuronal plasticity: adult
Low plasticity and low regenerative abilities
Is plasticity a more viable option for repair?
Axonal degeneration
Regeneration (we want this but not really happening)
Plasticity (can it take over? Usually more effective )
Development of the nervous system and the critical period
Critical period in nervous system: time during which reduction of neuronal numbers, remodelling of synapses and strengthening of connections occurs
Most influential time - permanent connections
Brain more plastic
