Nodal and paranodal structural changes in frog optic nerve during early Wallerian degeneration

Ultrastructural changes in the nodal and paranodal regions of myelinated nerve fibres of frog optic nerves were studied during early stages of Wallerian degeneration. The earliest changes seen include retraction of paranodal loops of myelin from the axolemma and disconnection of paranodal myelin loops from myelin lamellae. These paranodal changes are asymmetric around the node and may be more advanced on either the proximal or distal side. Axoplasmic changes, including segregation of microtubules from neurofilaments, disorientation of microtubules and accumulation of abnormal organelles at nodes, appear shortly. In some axons the 'undercoating' along the widened nodal surfaces becomes patchy, and blebs appear in the nodal axolemma. In freeze-fracture replicas a mixture of particle clusters and particle-free areas appears in both E- and P-faces of the nodal axolemma. Blebs remain particle free. Initially, E-face particles remain segregated to the node and are present only at much lower concentrations in the demyelinated paranodal axolemma, suggesting that they are not freely mobile at this stage. Nodal E-face particles begin to decrease on day 5 associated with an increase in particles at the adjacent demyelinated paranode, and by day 11 the particle distribution is uniformly low over the entire extent of the nodal and demyelinated paranodal axolemma. If nodal E-face particles represent sodium channels, as has been proposed, the sequence of changes in Wallerian degeneration would be compatible with a gradual redistribution of nodal sodium channels into the demyelinated paranode.