Absence of a permissive substrate for growth is not, however, the only factor responsible for the failure of Charlestown, Massachusetts 02129 central axons to regenerate (Schwab and Bartholdi, 1996). Three other issues are important: survival of the injured neurons (Coggeshall et al., 1997), the capacity Summary of adult neurons to recapitulate those developmental processes that enable neurite formation and outgrowth, Regeneration is abortive following adult mammalian i.e., their intrinsic growth state (Chong et al., 1996), and, CNS injury. We have investigated whether increasing finally, the formation of impenetrable barriers at the lethe intrinsic growth state of primary sensory neurons sion site (Jakeman and Reier, 1991). by a conditioning peripheral nerve lesion increases Those DRG neurons whose axons ascend in the dorsal regrowth of their central axons. After dorsal column columns provide a useful model system to examine lesions, all fibers stop at the injury site. Animals with central regeneration. First, these cells do not die after a peripheral axotomy concomitant with the central leperipheral or central axonal injury (Coggeshall et al., sion show axonal growth into the lesion but not into 1997). Second, injuring the peripheral but not the centhe spinal cord above the lesion. A preconditioning tral axons of these cells changes their intrinsic growth lesion 1 or 2 weeks prior to the dorsal column injury state (Schreyer and Skene, 1993; Chong et al., 1994). results in growth into the spinal cord above the lesion. This can be seen in vitro where an increased growth In vitro, the growth capacity of DRG neurite is also state can be detected after nerve lesions in dissociated increased following preconditioning lesions. The incells or explant DRG cultures (Hu-Tsai et al., 1994; Edtrinsic growth state of injured neurons is, therefore, a strom et al., 1996; Smith and Skene, 1997). In vivo, induckey determinant for central regeneration. ing peripheral nerve-conditioning lesions at the same time as implanting peripheral nerve grafts immediately adjacent to injured central axons of primary sensory