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Abstract
Several experimental manipulations result in axonal regeneration in the central nervous
system (CNS) when applied before or at the time of injury but not when initiated after
a delay, which would be clinically more relevant. As centrally injured neurons show
signs of atrophy and degeneration, it raises the question whether chronically injured
neurons are able to regenerate. To address this question, we used adult rodent primary
sensory neurons that regenerate their central axon when their peripheral axon is cut
(called conditioning) beforehand but not afterwards. We found that primary sensory
neurons express regeneration-associated genes and efficiently regrow their axon in
cell culture two months after a central lesion upon conditioning. Moreover, conditioning
enables central axons to regenerate through a fresh lesion independent of a previous
central lesion. Using in vivo imaging we demonstrated that conditioned neurons rapidly
regrow their axons through a fresh central lesion. Finally, when single sensory axons
were cut with a two-photon laser, they robustly regenerate within days after attaining
growth competence through conditioning. We conclude that sensory neurons can acquire
the intrinsic potential to regenerate their axons months after a CNS lesion, which
they implement in the absence of traumatic tissue.