Observations on the progress of Wallerian degeneration in transected peripheral nerves of C57BL/Wld mice in the presence of recruited macrophages

Summary

The first part of this study is a description of the effect of the intraneural injection of lysophosphatidyl choline into the sciatic nerves of C57BL/Wld mice. This mouse is unusual because its peripheral nerve fibres degenerate very slowly after transection, and few myelomonocytic cells are recruited into the endoneurium after traumatic injury. However, intraneural injection of lysophosphatidyl choline produced a typical demyelinating lesion in which recruited macrophages were active in removal of myelin. In the second part of the study, nerves were transected either before, at the same time as, or some days after, the intraneural injection of lysophosphatidyl choline into the distal stump; the changes within the endoneurium were compared with those seen in distal stumps which had not been injected with lysophosphatidyl choline. Immunohistochemical and ultrastructural examination during the period 1–4 weeks after transection showed that degeneration occurred in the portion of each nerve which had been injected with LPC (and which therefore contained exogenous macrophages) but failed to occur in the portion of nerve which was not penetrated by the injected bolus of lysophosphatidyl choline. It is suggested that the unusual property of sealing off of the tips of the transected axons within the distal stumps may be a significant factor in maintaining ‘normal’ Schwann cell-axon relationships along transected axons, even though the axons are separated from their cell bodies. Lysophosphatidyl choline destabilises the Schwann cell-axon relationship by initiating myelin breakdown within the Schwann cell. It is suggested that while the Schwann cells remain closely associated with the axons in the distal stumps, they do not behave as denervated cells and consequently may be incapable of signalling their damaged status.