A conditioning lesion induces changes in gene expression and axonal transport that enhance regeneration by increasing the intrinsic growth state of axons

Injury of axons in the peripheral nervous system (PNS) induces transcription-dependent changes in gene expression and axonal transport that promote effective regeneration by increasing the intrinsic growth state of axons. Regeneration is enhanced in axons re-injured 1-2 weeks after the intrinsic growth state has been increased by such a prior conditioning lesion (CL). The intrinsic growth state does not increase after axons are injured in the mammalian central nervous system (CNS), where they lack the capacity for effective regeneration.Sensory neurons in the dorsal root ganglion (DRG) have two axonal branches that respond differently to injury. Peripheral branches, which are located entirely in the PNS, are capable of effective regeneration. Central branches regenerate in the PNS (i.e., in the dorsal root, which extends from the DRG to the spinal cord), but not in the CNS (i.e., the spinal cord). A CL of peripheral branches increases the intrinsic growth state of central branches in the dorsal columns of the spinal cord, enabling these axons to undergo lengthy regeneration in a segment of peripheral nerve transplanted into the spinal cord (i.e., a peripheral nerve graft). This regeneration does not occur in the absence of a CL. We will examine how changes in gene expression and axonal transport induced by a CL may promote this regeneration.