Axonal degeneration

Axonal degeneration is the result of primary destruction of the axon, with secondary disintegration of its myelin sheath.

- Damage to the axon may be due to either:

1- a focal event occurring at some point along the length of the nerve (such as trauma or ischemia) or
2- more generalized abnormality affecting the neuron cell body
(neuronopathy) or its axon (axonopathy).
- When axonal injury occurs
as the result of a focal lesion, ( such as traumatic transection of a nerve), the distal
portion of the fiber undergoes Wallerian degeneration

- Within a day,
the axon breaks down, and Schwann cells begin to degrade the myelin and then
engulf axon fragments, forming small oval compartments (myelin ovoids).
Macrophages are recruited into the area and participate in the phagocytosis of
axonal and myelin-derived debris.

N.B. In the slowly evolving neuronopathies or axonopathies, evidence of myelin breakdown is scant
because only a few fibers are degenerating at any given time.

The stump of the proximal portion of the severed nerve shows degenerative changes
involving only the most distal two or three internodes and then undergoes regenerative activity.

The affected muscles fibers :

- When axonal degeneration occurs, the muscle fibers within the affected motor unit lose their neural input and undergo
denervation atrophy.
- Denervation of muscle leads to breakdown of myosin and actin, with a decrease in cell size and resorption of myofibrils, but cells
remain viable.
- In cross-section:
The atrophic fibers are smaller than normal and have a roughly triangular (“angulated”) shape.
There is also cytoskeletal reorganization of some muscle cells, which results in a rounded zone of disorganized
myofibers in the center of the fiber (target fiber).

• Nerve regeneration :
- The proximal stumps of degenerated axons can develop new growth cones as the axon regrows.
- These growth cones will use the Schwann cells vacated by the degenerated axons to guide them,

The presence of multiple closely aggregated thinly myelinated small-caliber axons is evidence of regeneration (regenerating cluster)

- Regrowth of axons is a slow process, on the order of 1 to 2 mm per day,

- Apparently limited by :
1- the rate of the slow component of axonal transport,
2- the movement of tubulin, actin, intermediate filaments.
Despite its slow pace, axonal regeneration accounts for some of the functional recovery after nerve injury and can be
accelerated with marrow stromal cell transplants.

• Re - innervation of the muscle :

- The reinnervation of skeletal muscle changes its composition, altering the distribution of the two major types of fibers, type 1 and type 2.
The fiber types are determined by the neuron of the motor unit,
Type 1 fibers Type 2 fibers
high in myoglobin & oxidative enzymes & have many mitochondria Type 2 fibers are rich in glycolytic enzymes
in keeping with their ability to perform tonic contraction; and are involved in rapid phasic contractions;
they are dark staining on ATPase stain performed at pH 4.2 they are dark staining on ATPase stain performed at pH 9.4
but light staining at pH 9.4. but light staining at pH 4.2.

- Since the motor neuron determines fiber type, all muscle fibers of a single unit are of the same type.
- The fibers of a single motor unit are distributed across the muscle, giving rise to a checkerboard pattern of alternating fiber types, as is
demonstrated especially well with staining for ATPase .

Normally, there is some variability in the relative abundance of type 1 and type 2 fibers among different muscles.