Degeneration and repair of the peripheral nervous system

Question 1

What is significant about the population of neurones in our body?

Answer 1

We are born with all the neurones we will ever have.

Question 2

What are the effects of ALS (motorneurone disease)?

Answer 2

• Causes degeneration of motor neurones.

- Leads to progressive paralysis.

Question 3

What are the effects of Friedreich’s ataxia?

Answer 3

• Causes sensory neurone degeneration.

- Leads to progressive loss of motor function.

Question 4

What are the effects of poliomyelitis?

Answer 4

• Motor neurones are infected by the virus.

- Leads to progressive muscle weakness and paralysis.

Question 5

What are the effects of syphilis?

Answer 5

• Causes degeneration of the sensory neurone dorsal root ganglia.
• Leads to loss of somatosensation (tabes dorsalis).

Question 6

What are common demyelinating peripheral neuropathies?

Answer 6

• Charcot-Marie-Tooth disease: Causes muscle weakness, wasting and loss of sensation.
• Guillain-Barre syndrome: Autoimmune attack on myelin with similar symptoms to MS, but is transient.

Question 7

What are the common mechanical causes of axon damage?

Answer 7

1. Compression
2. Trauma (compression/tearing) due to fractures
3. Trauma (compression/tearing) due to joint dislocation
4. Avulsion (pulling away) of spinal roots

Question 8

What are the common causes of nerve compression?

Answer 8

1. Swelling (e.g. of local tendons in carpal tunnel syndrome)
2. Tumours
3. Prolapsed intervertebral disc

Question 9

What are the common causes of trauma-related nerve injuries?

Answer 9

1. Fractures

2. Dislocations

Question 10

What are the common causes of peripheral neuropathies?

Answer 10

Inadequate blood supply, e.g. frostbite, ischaemia, diabetes, leprosy…

Question 11

What is the main difference between local and systemic nerve damage?

Answer 11

Systemic nerve damage produces bilateral loss of function while local nerve damage only causes unilateral loss of function.

Question 12

What did River and Head show?

Answer 12

If a severed nerve is re-sutured, restoration of function is possible and nerves can regrow at rate of up to 1 mm/day.

Question 13

What causes Wallerian degeneration?

Answer 13

Electrical/mechanical isolation of distal parts of axon from the soma of the neurone. This can occur as a result of compression/lesion.

Question 14

What is the process of Wallerian degeneration?

Answer 14

1. Distal axon breaks down and myelin degenerates.
2. Schwann cells carry out phagocytosis to clear axon/myelin debris.
3. Schwann cells release neurotrophins that promote axon regeneration and guide the regenerating axon by chemotaxis.
4. Soma of cells undergo chromatolysis (dissolution of Nissl substance) to support axon growth.
5. As axon grows, Schwann cells form new myelin around new axon.

Question 15

How do axons grow?

Answer 15

• They develop growth cones.
• These growth cones use contact and chemotaxis to guide the growth of axons.
• These cones use a combination of repel signals and attract signals to determine direction of growth.

Question 16

What are the limitations of axon regeneration?

Answer 16

1. Incorrect connections are made. For example, motor neurones innervate skin and sensory neurones innervate muscle.
2. Regenerated neurones may not innervate structures in same way as originally.
3. Neurones may make connections to each other (neuroma).

Question 17

What are the factors that affect axon regeneration?

Answer 17

1. Extent of damage: Extent of damage and disruption to connective tissue layers.
2. Speed of regrowth: Axons can only regrow at rate of 1 mm/day.
3. Time: Regrowth of axons rely on communication between axon and Schwann cells (via trophic factors). Target tissues also make trophic factors affecting growth. If axon doesn’t reconnect within weeks, it atrophies and ceases to produce trophic factors. This prevents axon regrowth. This limits the distance of lesion.
4. Gaps: Axons are unable to grow across gaps. This means that 2 cut ends of a nerve need to be re-sutured or nerve graft needs to be used to bridge gap.
5. Accuracy: The greater the distance, the less accurate the axons are regenerated.

Question 18

What are the future prospects of nerve repair?

Answer 18

1. Stem cells may be used to produce trophic factors that can be introduced to encourage axon regeneration.
2. Stem cells can be used as gap-bridging tissue (instead of nerve graft).
3. Stem cells may be used to prevent atrophy of target tissue and extend time window.
4. Stem cells may be used to more accurately target growing axons.