Chapter 1 : The Cells of the CNS

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Peripheral Nerve Injury, Regeneration and Degeneration

Regeneration of Peripheral Nerve Axons after Damage

Nerve injury usually occurs as a result of pressure, blunt injury or transection, and the severity and duration of the symptoms depends on the degree of damage inflicted.

The milder degrees of nerve injury produce transient symptoms without the effects of complete transection of the axon.

Symptoms arising from pressure on nerves include weakness of the muscles that are innervated, and sensory symptoms of tinglings, numbness or lack of sensation.

Neurapraxia is a condition where pressure on the nerve reduces bood flow and may cause some damage to myelin, resulting in a transient block of action potentials. The effects on nerve conduction are reversible and transient.

Axonotmesis is more severe that neurapraxia., and causes conduction block in the axon. If the axon degenerates, time is needed for the axons to grow back through their endoneurial sheaths to reinnervate the muscle and sensory endings they had done originally.

Neurotmesis is the most severe injury, with axons and the nerve sheath being severed. Axons develop growth cones but do not necessaily grow along their original fasciculi, and may reinnervate targets other than the original ones.


The diagram shows the structure of a peripheral nerve.

A connective sheath, the epineurium, surrounds each spinal nerve, and the nerve fibres are arranged in bundles called fasciculi.

Each fasciculus has a membrane around it (the perineurium) and each axon is supported by a tube of connective tissue - the endoneurium.


Neurones in the peripheral nervous system are able to regrow and reinnervate their taget organs after injury to their axons, whereas damage within the CNS is not normally associated with the ability to regenerate axons.




Neuronal Changes during Regeneration

Neuronal damage can take several forms, e.g. the death of neurones in viral infections, such as poliomyelitis, or the degeneration of specific types of neurones, such as in motoneurone disease, or the degeneration of the nigro-striatal pathway in Parkinson's Disease.

Neurones in the peripheral nervous system are able to regrow and reinnervate their taget organs after injury to their axons, whereas damage within the CNS is not normally associated with the ability to regenerate axons.

This section deals with the responses that follow damage to axons in peripheral nerves.

Axons in peripheral nerves can be damaged by pressure or transection, but can often regenerate and grow back to their target organs.

In the days following nerve transection:

  1. the peripheral end of the axon degenerates,

  2. the central end of the transected axon begins to sprout and develop growth cones

  3. the nerve cell body undergoes a process called chromatolysis


The diagram shows the events following axonal transection.

  1. Some Schwann cells become phagocytic and engulf degenerating axon and myelin.
  2. The central end of the axon sprouts and the sprouts grow into the endoneuial sheaths left behind by the degenerated terminal portion of the original axon
  3. Schwann cells proliferate as the axon grows towards the muscle
  4. The axon re-establishes contact with the muscle fibre. At this stage the axon is quite fine and not yet fully myelinated
  5. The terminal axon increases in diameter due to the production of new neurofilaments that increase the axonal diameter; and the terminal axon becomes myelinated.
  6. It may be that the distal portion of the regenerated axon never reaches the diameter or degree of myelination of the original axon, as the conduction velocity does not necessarily return to its previous level

  7. If regeneration of axons fails, then the muscle fibre atrophies, and the neuronal cell body degenerates and undergoes apoptosis.

  8. After the nerve transection, the neuronal cell body undergoes a process of chromatolysis, in which the nucleus of the cell moves to one side, away from the centre of the perikaryon; and the Nissl Substance (RNA) disaggregates and is much reduced.

  9. At this point in time the protein synthesis in the cell changes so that the proteins required for the axonal growth are manufactured, packaged and transferred to the growing terming by means of anterograde axonal transport.

In peripheral nerves, axonal regrowth takes place at the rate of approximately1 cm / week in humans. This is possible because macrophages remove cellular debris, and no inhibitory substances are present.

In contrast in the CNS, no macrophages are there to clear the cellular debris, and some powerful inhibitory molecules are present that prevent the regrowth of axons. Thus nerve regeneration is limited in the CNS.

In the CNS the lack of macrophages causes reactions from astrocytes which results in scarring.


Regenerating nerve terminals are fine and much smaller than the normal axons. Once a regenerating neurone has contacted its post-synaptic cell, the axon expands, due to the synthesis of neurofilaments that are regulate the diameter of axons. These changes result in the speed of conduction of nerve impulses returning towards their normal level.




The Formation of Lerge Motor Units after nerve damage


The images show motor units in different situations.

Following nerve transection, some axons regenerate and make new connections with the muscle fibres.

When reinnervation occurs it is not uncommon to find that one axon innervates more muscle fibres in a small area of muscle than previously, resulting in an increase in the size of the motor unit. The size of motor units and the presence of denervated muscle fibres can be examined using Electromyography.



Clinical Assessment of Nerve Regeneration

Axons in the peripheral nervous system are, given the right conditions, able to regenerate after damage or transection, resulting in restortion of function.

Axons in the central nervous system rarely regenerate.

Tinel's (or Hoffmann's) Test

Regenerating sensory axons can be followed clinically because the growing terminals are sensitive to pressure. Tinel's Test makes use of this and the diagram shows the action of tapping the nerve. The patient reports feeling transient tinglings in the peripheral cutaneous field of the nerve when the nerve is tapped through the skin.

The test can be used to trace the rate of growth of the sensitive nerve terminals as regeneration progresses.

The median nerve can become damaged in the Carpal Tunnel, and Tinel's sign can be used as a test for this condition. Sometimes instead of tapping continuous pressure can also elicit sensory symptoms.

While Tinel's sign is a useful clinical test, clinical neurophysiological testing provides a much clearer picture of the state of degeneration and reinnervation of muscle.



Clinical Neurophysiology Tests

Nerve Conduction Tests
Evoked Potentials


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