Lecture 30- Injury to the nervous system I

Question 1

What are the general differences between the CNS and the PNS?

Answer 1

-if a neuron is in the CNS it will not be repaired but in the PNS it will

Question 2

What are the types of peripheral and central projections?

Answer 2

• 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

Question 3

What happens in the PNS when an axon is damaged?

Answer 3

-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

Question 4

What happens in the CNS when an axon is damaged?

Answer 4

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

Question 5

What was the case of Henry Head?

Answer 5

-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

Question 6

What does the repair of axons in PNS depend on?

Answer 6

-depending on the severity and location of the PNS injury, there may full or partial repair

Question 7

What is the difference between CNS and PNS that allows the PNS to regenerate?

Answer 7

– Structure

– Cell types

– Molecules and guidance/repellent cues

Question 8

What is the structure of a peripheral nerve like?

Answer 8

• 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

Question 9

What does a normal motor neuron look like?

Answer 9

Normal neuron/nerve fibre

• Central nucleus
• Dense Nissl substance

Question 10

What happens if a motor neuron is damaged? (2 weeks post injury)

Answer 10

-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

Question 11

What happens if a motor neuron is damaged? (3 weeks post injury)

Answer 11

-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

Question 12

What happens if a motor neuron is damaged? (3 months post injury)

Answer 12

• Successful Regeneration
• Electrical activity restored= Muscle fibre regeneration

-muscle is contractile again and the neuron is re-myelinated and pretty functional

Question 13

What happens when the regeneration is not successful?

Answer 13

-sometimes regeneration doesn’t happen, crushed etc. they grow but form a neuroma (hurts!)

Question 14

What is the importance of basal lamina in PNS regeneration?

Answer 14

-basal lamina cylinder remains even when the inside neuron is gone, and act as a guidework for the new neurites

Question 15

What is a growth cone?

Answer 15

-the motile end of a growing axon

– responds to signals in the environment

Question 16

What are some aspects that are important for the regeneration?

Answer 16

• 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

Question 17

What are the molecular and cellular response that promote peripheral nerve regeneration?

Answer 17

-

Question 18

What is the importance of Schwann cells for peripheral nerve repair?

Answer 18

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)

Question 19

What are some other changes that occur in regrowing axons?

Answer 19

• 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

Question 20

What is the importance of regeneration of peripheral synapses?

Answer 20

-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

Question 21

How does reinnervation of muscles following peripheral motor nerve damage occur?

Answer 21

• 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

Question 22

Is there specificity to the growth factors and their targets?

Answer 22

• Different neuronal types require different growth factors
• different growth factors depending on where the neurons are, so can help when applying the right factors

Question 23

What are some of the issues with re-innervating synapses after PNS damage?

Answer 23

• 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

Question 24

How is regeneration affected by the type of injury (cut/crush)?

Answer 24

-crush is better as basal lamina is still intact and can act as a guide

Question 25

When is axonal repair faster: cut or crush?

Answer 25

-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

Question 26

Does exercise affect the peripheral nerve regeneration time?

Answer 26

-Regeneration in peripheral nerves is faster with exercise

Question 27

What is this?

Answer 27

• 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