Wallerian degeneration occurs when a nerve fiber is crushed, frozen, or cut and degeneration of part of the axon distal (the part of the nerve that’s furthest away from the neuron’s cell body) begins.

This process happens in both the peripheral nervous system (PNS) and the central nervous system (CNS) but how the nerves are repaired after injury in these two systems is very different.

This process is also referred to as “anterograde degeneration.”

Below, we’ll explore what Wallerian degeneration is, how it differs in PNS and CNS, and what the symptoms of this natural process are.

The History of Wallerian Degeneration

The term Wallerian degeneration refers to Augustus Volney Waller, who first described the degeneration process of severed nerves.

In 1850, Waller began experimenting on frogs, severing their hypoglossal and glossopharyngeal nerves. He observed the site of injury and the distal nerves, describing how the myelin (which he called “medulla”) disintegrated into various sizes of separated particles. He was able to stain the degenerated axons to allow scientists to study individual nerve fibers and their courses.

What Happens During Wallerian Degeneration?

When there’s a cut to an axon, the axon neuron cell body becomes separate to the axon distal. Therefore, the process of Wallerian degeneration is when this separated axon degenerates away from the site of the injury.

After the lesion happens, the axon tends to degenerate within 24-36 hours – but prior to this, the distal axon may still be electrically excitable.

When there is an axonal injury in both the central nervous system (CNS) and the peripheral nervous system (PNS), Wallerian degeneration occurs. However, as mentioned previously, the degeneration of the axon occurs very differently in the two different types of nervous systems.

Wallerian Degeneration: PNS vs CNS

In the peripheral nervous system, degeneration is triggered when axonal debris and myelin are removed by macrophages that have entered the injured area. The membrane of the axon breaks apart and its skeleton disintegrates.

However, the outer layer of the axon’s neuron, which is constructed from Schwann cells (the neurolemma), doesn’t degenerate and retains its tube-like shape. Within approximately 96 hours of the injury, this hollow tube of Schwann cells begins to synthesize growth factors. At the distal end of the injured axon, this process starts to attract axonal spouts – these originate at the severed axon’s proximal end.

If an axon sprout is successful in reaching the neurolemma, it starts to grow into it and will advance at around 1mm per day, which is the equivalent of 3cm per month. Consequently, these tubes provide sprouting axons (aka regenerating axons) with pathways, allowing them to follow the skin and muscles. Then, the Schwann cells work on the formed axons to remyelinate them, and these eventually innervate (supply nerves to) the targeted tissue.

However, the myelin that is formed is often thinner than normal and the tubes created are shorter than normal.

The Difference in CNS

In contrast, axonal regeneration occurs far slower in the CNS. And the primary reason for this is because oligodendrocytes produce the myelin sheaths – not Schwann cells (this includes the spinal cord).

When it comes to removing myelin debris from the CNS this happens slowly (taking around 2-4 weeks after the injury has been sustained) because it takes the macrophages this long to remove all of the particles. This slower regeneration process is due to the myelin debris containing inhibitory factors.

Later on, pathways for axonal growth are blocked by astrocytic scars which are formed in the transected area when astrocytes proliferate it.

The Symptoms of Wallerian Degeneration

The symptoms you experience if your body is going through Wallerian degeneration will be different depending on the type of injury you have and which nervous system is involved. However, there are a number of potential signs and symptoms that could indicate you have sustained an injury to one of your nerves (in either the PNS or the CNS). These include:

  • Weakness, numbness, tingling, or the inability to move all of one side or part of your body
  • Loss of vision, double vision, blurring, or dimness in one or both of your eyes
  • Trouble understanding speech, difficulty talking, or loss of speech
  • A severe headache that comes on suddenly
  • The inability to walk or stand, unsteadiness, or dizziness
  • A change in your behavior or consciousness, moments of confusion
  • Severe vomiting or nausea
  • Shooting, stabbing, or burning pains in the affected area

Some of these symptoms tend to be constant, but others may come and go.

If you do experience any of these symptoms or you’ve sustained an injury, it’s important to seek the advice of your doctor as soon as possible. The treatment required will depend on where the nerve is located and the extent of the damage caused. It may require surgery and your brain may need “re-educating” to use the nerve properly again – this is sometimes teamed with physical therapy, too.

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