Wallerian Degeneration - Notes

Definition

Where it occurs

• Affects the axon distal to the site of injury, up to the next node of Ranvier proximally.
• The distal segment degenerates because it has lost its connection with the cell body (soma), which is the source of proteins and metabolic support needed to sustain the axon.
• • Ganong's Review of Medical Physiology, 26th ed.

Sequence of Events

1. Axoplasmic transport failure - within hours of injury, axonal transport stops in the distal stump.
2. Axon breakdown - the distal axon swells and then fragments into small ovoid pieces (days 1-3).
3. Myelin sheath degeneration - the myelin sheath surrounding the distal axon breaks down and degenerates in parallel with axon fragmentation.
4. Macrophage/Schwann cell clearance - Schwann cells proliferate and, along with infiltrating macrophages, phagocytose (clear away) the axonal and myelin debris.
5. Formation of Bands of Büngner - proliferated Schwann cells arrange themselves in longitudinal columns within the persisting basal lamina tube, forming a scaffold that guides subsequent axonal regeneration.

• • Medical Physiology, Box 10-3 "Axonal Degeneration and Regeneration"

Changes in the Cell Body (Chromatolysis)

• The cell body swells.
• The nucleus becomes eccentrically placed.
• The endoplasmic reticulum (Nissl substance) fragments and disperses.
• • Ganong's Review of Medical Physiology, 26th ed.

Proximal Segment

• The proximal stump (still attached to the cell body) may show a limited amount of degeneration back to the nearest node of Ranvier, but then stabilizes and begins the process of regeneration (sprouting) if the cell body survives.

Time Course

• Degeneration changes are typically evident within days and are essentially complete over 1-3 weeks in peripheral nerves (clinically, nerve conduction studies show loss of the distal compound action potential once Wallerian degeneration is complete, around 7-11 days for motor fibers and slightly longer for sensory fibers).

Clinical/Functional Significance

• Because the axon and myelin distal to the lesion degenerate, nerve conduction is lost distal to the injury — this is why electrodiagnostic testing (nerve conduction studies/EMG) shows conduction block or absent responses distal to a site of axonal injury once Wallerian degeneration has occurred.
• The process clears debris and preserves the endoneurial tube/basal lamina, which is essential for successful axonal regeneration in the peripheral nervous system (Schwann cells and the Büngner bands guide the regrowing axon back toward its target).
• In the CNS, Wallerian degeneration also occurs but functional regeneration is far more limited because oligodendrocytes and CNS myelin do not support regrowth the way Schwann cells do, and inhibitory molecules in CNS myelin debris additionally block regrowth.
• Used experimentally/clinically as a basis for anterograde axonal tracing techniques since degenerating axoplasm can be histologically stained.

Summary Table