Figure 1.

Course of Wallerian axon degeneration. As early as 5–30 min after nerve injury, the axonal segments proximal (left) and distal (right) to the injury site exhibit short-distance acute axon degeneration (AAD), an event that is principally mediated by extracellular Ca²⁺ influx and activation of the intracellular Ca²⁺-dependent protease calpain. This event is followed by a slower axonal retraction and formation of axonal bulbs at the injury sites (arrowheads). For the next 24 to 48 h after injury there is a period of relative latency in which the distal axon remains morphologically stable and electrically excitable. Although beading occurs along the distal axon at irregular intervals, there are few signs of physical fragmentation. At more than 72 h after injury, rapid fragmentation and cytoskeletal breakdown occur along the full length of the distal axon, followed by increased glial (consisting primarily of astrocytes, macrophages and, in the PNS, Schwann cells) influx to clear axonal remnants (blue circles) and to possibly promote regenerative attempts by the proximal axon.