False resurrections: distinguishing regenerated from spared axons in the injured central nervous system

Several recent studies report that axon regeneration can be induced in the mature mammalian nervous system by novel treatments or genetic manipulations. In assessing these reports, it is important to be mindful of the history of regeneration research, which is littered with the corpses of studies that reported regeneration that later proved incorrect. One important reason is the "spared axon conundrum," in which axons that survive a lesion are mistakenly identified as having regenerated. Here, we illustrate the problem and propose criteria that may be used to identify regenerated vs. spared axons, focusing on the injured spinal cord.