Some retrograde degeneration also occurs in the proximal axon and is called traumatic degeneration. This process appears to be histologically similar to antegrade (Wallerian) degeneration. The coverage of traumatic degeneration depends on the severity of the injury and usually extends for only one or a few internodal segments. Sometimes, traumatic degeneration extends more proximally than one or a few nodes of Ranvier and may result in death of the cell body. When a motor fiber is cut, the muscle innervated by that fiber undergoes atrophy (Fig. 12.33c).
Retrograde signaling to the cell body of an injured nerve causes a change in gene expression that initiates reorganization of the perinuclear cytoplasm.
Axonal injury also initiates retrograde signaling to the nerve cell body leading to the upregulation of a gene called c-jun. C-jun transcription factor is involved in early as well as later stages of nerve regeneration. Reorganization of the perinuclear cytoplasm and organelles starts within a few days. The cell body of the injured nerve swells, and its nucleus moves peripherally. Initially, Nissl bodies disappear from the center of the neuron and move to the periphery of the neuron in a process called chromatolysis. Chromatolysis is first observed within 1 to 2 days after injury and reaches a peak at about 2 weeks (see Fig. 12.33b). The changes in the cell body are proportional to the amount of axoplasm destroyed by the injury; extensive loss of axoplasm can lead to death of the cell.
Before the development of modern dyes and radioisotope tracer techniques, Wallerian degeneration and chromatolysis were used as research tools. These tools allowed researchers to trace the pathways and destination of axons and the localization of the cell bodies of experimentally injured nerves.
In the PNS, Schwann cells divide and develop cellular bands that bridge a newly formed scar and direct growth of new nerve processes.
As mentioned above, division of dedifferentiated Schwann cells is the first step in the regeneration of a severed or crushed peripheral nerve. Initially, these cells arrange themselves in a series of cylinders called endoneurial tubes. Removal of myelin failure of axon regeneration
FIGURE 12.34 • Schematic diagram of response to neuronal injury within peripheral and central nervous systems. Injuries of nerve processes (axons and dendrites) both in PNS and CNS induce axonal degeneration and neural regeneration. These processes involve not only neurons but also supportive cells such as Schwann cells and oligodendrocytes, as well as phagocytic cells such as macrophages and microglia. Injuries to axons in PNS lead to their degeneration, which accompanies divisions and dedifferentiation of Schwann cells and disruption of the blood–nerve barrier along entire length of the injured axon. This allows massive infiltration of monocyte-derived macrophages, which are responsible for the process of myelin removal. Rapid clearance of myelin debris allows for axon regeneration and subsequential restoration of blood–nerve barrier. In the CNS, limited disruption of the blood–brain barrier restricts infiltration of monocyte-derived macrophages and dramatically slows the process of myelin removal. In addition, appoptosis of oligodendrocytes, an inefficient phagocytic activity of microglia, and the formation of an astrocyte-derived scar lead to failure in nerve regeneration in the CNS.