Lecture 30- Injury to the nervous system I Flashcards
What are the general differences between the CNS and the PNS?
-if a neuron is in the CNS it will not be repaired but in the PNS it will
What are the types of peripheral and central projections?
- CNS to CNS is the most common in the CNS, some CNS to motor (so PNS)
- Peripheral and Central
- Projections:
1. Central to Central
2. Central to Peripheral
3. Peripheral to Peripheral
What happens in the PNS when an axon is damaged?
-the proximal part can regrow into the damages spot and connect again
• When peripheral axons (ie nerves) are damaged the proximal portion of the axon can regenerate into the damaged distal region
- Neuron cell body can be in a peripheral ganglion or in the CNS
- May be full but often partial repair
What happens in the CNS when an axon is damaged?
When central axons or neurons are damaged
- Some neurons die
- Some neurons retract processes but can “sprout” and make new local connections In some CNS regions neural stem cells can make new neurons and replace dead neurons
- Normally not very effective following injury in mammals – current focus of research
What was the case of Henry Head?
-Cut nerves and monitored return of sensation and movement to his hand over 2 years
- Some return of general sensation to pressure and touch returned by 6-20 weeks
- Slower and incomplete recovery of sense of light touch, temperature, pinpricks, 2-point discrimination and fine motor control – did not fully recover by 2 years
- Indicates differences in regenerative capacity between different DRG sensory neurons as well as spinal motor neurons
What does the repair of axons in PNS depend on?
-depending on the severity and location of the PNS injury, there may full or partial repair
What is the difference between CNS and PNS that allows the PNS to regenerate?
– Structure
– Cell types
– Molecules and guidance/repellent cues
What is the structure of a peripheral nerve like?
- made up of both motor and sensory axons
- sensory going through DRG (dorsal)
- motor in ventral
- the neuronal fibres are usually myelinated by Schwann cells
What does a normal motor neuron look like?
Normal neuron/nerve fibre
- Central nucleus
- Dense Nissl substance
What happens if a motor neuron is damaged? (2 weeks post injury)
-2 weeks post-injury
- Peripheral nucleus
- loss of Nissl substance - (chromolysis/chromatolysis) Wallerian Degeneration
- Degeneration of axon and myelin sheath below site of injury
- Debris phagocytosed by macrophages
- cell body looks really weird, pale looking, chromolysis
- then Wallerian degeneration happens
- Muscle fibre atrophy
What happens if a motor neuron is damaged? (3 weeks post injury)
-3 weeks post-injury
- Schwann cells proliferate, forming a compact cord
- Growing axons penetrate the Schwann cell cord –grow at 0.5-3mm/day
- Muscle fibre atrophy
- Schwann cells proliferate like mad -the debris is basically gone by then
What happens if a motor neuron is damaged? (3 months post injury)
- Successful Regeneration
- Electrical activity restored= Muscle fibre regeneration
-muscle is contractile again and the neuron is re-myelinated and pretty functional
What happens when the regeneration is not successful?
-sometimes regeneration doesn’t happen, crushed etc. they grow but form a neuroma (hurts!)
What is the importance of basal lamina in PNS regeneration?
-basal lamina cylinder remains even when the inside neuron is gone, and act as a guidework for the new neurites
What is a growth cone?
-the motile end of a growing axon
– responds to signals in the environment
What are some aspects that are important for the regeneration?
- Schwann cells and macrophages are critical for promoting peripheral nerve regeneration
- once the debris is removed the Schwann cells start to proliferate
- Macrophages (phagocytic cells from blood) remove debris
- Schwann cells support intact axons and form peripheral myelin
- Schwann cells secrete molecules required for successful regeneration
What are the molecular and cellular response that promote peripheral nerve regeneration?
-
What is the importance of Schwann cells for peripheral nerve repair?
Schwann cells: create a molecular environment that supports axon guidance and growth
- secrete extracellular matrix molecules such as laminin, fibronectins and collagen to provide a structural support
- increase expression of cell surface molecules such as L1, N-CAM, N- cadherin, which bind to receptors on regenerating axons
- near the site of injury increase expression of neurotrophic factors such as Brain-derived neurotrophic factor (BDNF)
What are some other changes that occur in regrowing axons?
- actin and microtubule cytoskeleton dynamics increase
- expression of growth promoting proteins increases
eg - GAP43 (Growth Associated Protein 43) in growth cones
- integrins to bind to ECM
What is the importance of regeneration of peripheral synapses?
-Regrowth of axons to peripheral targets is required but without regeneration of synapses, recovery does not occur
• must be at appropriate target tissue
-e.g. motor fibre to muscle, sensory neuron to skin
How does reinnervation of muscles following peripheral motor nerve damage occur?
- When skeletal muscle fibres are denervated the neuromuscular synaptic sites remain intact for weeks
- When the axon degenerates, the Schwann cells in the nerve and Acetylcholine receptors (AChR) and protein scaffolds in the post-synaptic neuromuscular junction (NMJ) remain in place
- Expression of secreted factors by Schwann cells and muscle fibres is increased (eg NGF and BDNF) to allow directed regrowth
Is there specificity to the growth factors and their targets?
- Different neuronal types require different growth factors
- different growth factors depending on where the neurons are, so can help when applying the right factors
What are some of the issues with re-innervating synapses after PNS damage?
- Axons and AChR (labels postsynaptic neuromuscular junctions)
- After injury the regenerated axon can reinnervate the same sites of AChR synapses in the NMJ with a similar pattern of innervation as prior to injury but can often also be less accurate
- inappropriate target matching
- fine tuning of numbers of synapses requires pruning of excess fibres
- depends on electrical activity
How is regeneration affected by the type of injury (cut/crush)?
-crush is better as basal lamina is still intact and can act as a guide
When is axonal repair faster: cut or crush?
-Repair is faster if axon is crushed rather than cut
- Schwann cells and extracellular matrix in distal segments provide a guide in both instances but is continuous in crush injury
- the more precise the alignment the better the recovery of regeneration and function
- microsurgery is the main therapeutic approach to PNS injury – reattach proximal and distal stumps or insert a nerve graft
Does exercise affect the peripheral nerve regeneration time?
-Regeneration in peripheral nerves is faster with exercise
What is this?
- Growth-promoting properties of peripheral nerve sheaths and Schwann cells facilitate growth of damaged axons in the CNS
- peripheral grafts into the CNS
- can get regrowth as long as environment is PNS and they then don’t leave though so an issue
