Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord

We have investigated the effects of nerve growth factor (NGF), brain-derive d neurotrophic factor (BDNF),and neurotrophin-3 (NT-3) on the intraspinal r egeneration of anterogradely labeled axotomized ascending primary sensory f ibers in the adult rat. These fibers were allowed to grow across a predegen erated peripheral nerve graft and back into the thoracic spinal cord. In co ntrol animals that had been infused with vehicle for two weeks into the dor sal column, 3 mm rostral to the nerve graft, essentially no fibers had exte nded from the nerve graft back into the spinal cord. The number of sensory fibers in the rostral end of the nerve graft was not significantly differen t between control and neurotrophin-infused animals. With infusion of NGF, 3 7 +/- 2% of the fibers at the rostral end of the graft had grown up to 0.5 mm into the dorsal column white matter, 30 +/- 2% up to 1 mm, 19 +/- 3% up to 2 mm and 8 +/- 2% up to 3 mm, i.e., the infusion site. With infusion of NT-3, sensory fiber outgrowth was similar to that seen with NGF, but with B DNF fewer fibers reached farther distances into the cord. Infusion of a mix ture of all three neurotrophins did not increase the number of regenerating sensory fibers above that seen after infusion of the individual neurotroph ins. These findings suggest that injured ascending sensory axons are respon sive to all three neurotrophins and confirm our previous findings that neur otrophic factors can promote regeneration in the adult central nervous syst em. (C) 1999 Elsevier Science B.V. All rights reserved.