The pathogenesis of reactive axonal swellings: role of axonal transport

The role of axonal transport in the pathogenesis of the axonal swellings which develop at the severed ends of transected axons was studied by electron microscopic (EM) autoradiography. Proteins carried by fast anterograde transport in rat sciatic nerves were labeled with [3H]-leucine or [3H]-fucose; [3H]-leucine, [3H]-fucose, and [125I]-tetanus toxin were used to label components of retrograde transport. After the labeling procedure, the nerves were ligated and 2 to 24 hours later the animals were perfused with fixatives. The axonal swellings in both the proximal and distal stumps contained densely packed membranous organelles. The transported radioactivity in the swellings was strictly associated with these organelles, particularly pleomorphic vesicles and branched tubules derived from smooth endoplasmic reticulum. The endogenous (tritiated) substances had a similar association with the organelle collections in both the proximal stump (fast anterograde transport) and in the distal stump (retrograde transport). The exogenous marker of retrograde transport (125I-tetanus toxin) had the same autoradiographic localization. These results suggest that fast anterograde and retrograde transport are very similar processes carrying predominantly membranous organelles and constituting a system of bidirectional fast transport. The accumulations of organelles in reactive swellings are interpreted as the consequence of the acute focal interruption of this system. Studies of axonal transport provide a means for investigation of the origin and fate of axonal organelles in pathologic processes.