Delayed induction of the cell body response and enhancement of regeneration following a condition/test lesion of frog peripheral nerve at 15 degrees C.

Axons subjected to a prior injury exhibit an enhanced regenerative capability following a subsequent lesion. This phenomenon, known as the 'conditioning effect' has been demonstrated in both central and peripheral axons from a variety of species, but the locus of enhancement has remained in doubt. Several reports have tentatively concluded that the effect involves processes located in the cell body of the injured axon, while other investigators have implicated local processes at the site of the injury. The present experiments made use of a previous observation, the apparent suppression of the cell body response in injured frog neurons when the animals are housed at 15 degrees C, to investigate the location of the conditioning effect. The effect occurred in frog neurons from animals at 25 degrees C in the presence of a cell body response. The prior (conditioning) lesion produced a significant increase in regeneration rate (12-17%) and a significant decrease in the latency to the onset of regenerative outgrowth (12%). In contrast, regeneration was initially unaffected by the earlier conditioning lesion when the frogs were kept at 15 degrees C. After a 26-30 day interval, however, the rate of regeneration increased by 27%, coincident with the appearance of chromatolysis in the injured cell bodies. The 'conditioned' axons also continued to elongate, in contrast to singly-lesioned axons at 15 degrees C, and eventually reinnervated their target muscles. The cell body appeared to be the primary locus of the 'conditioning effect' in these experiments. This conclusion was further examined by measuring regenerative outgrowth in 15 degrees C neurons in which a cell body response had been induced prior to the test lesion. This was accomplished by maintaining frogs at 25 degrees C for 7 days after the conditioning lesion. The animals were then returned to the 15 degrees C environment for an additional 7 days before producing the test lesion. With this paradigm, regenerative outgrowth was enhanced without the 26-30 day delay interval. These results also suggest that the conditioning effect stimulates processes in the cell body of the injured axon, but the experiments do not indicate which processes were affected.