Neutralizing antibodies against neurite growth inhibitor NI-35/250 do not promote regeneration of sensory axons in the adult rat spinal cord

Neutralization of the myelin-associated neurite growth inhibitors NI-35 and NI-250 by IN-1 antibodies can promote axonal regeneration of several types of central nervous neurons. Here, we investigated in adult rats whether IN -1 can promote regeneration of ascending sensory axons across a peripheral nerve bridge back into the spinal cord. IN-1 was administered by hybridoma cells injected in the cerebral cortex or thoracic cord, its presence confir med in tissue sections and cerebrospinal fluid, and its effectiveness demon strated in co-cultures of oligodendrocytes anti sensory neurons. With a two week infusion of control vehicle into the dorsal spinal cord 3 mm rostral to the nerve graft, only 3 +/- 2% of the anterogradely labeled sensory fibe rs present at the rostral end of the nerve graft had grown up to 0.5 mm, bu t not farther into the spinal cord. A similar limited extent of regeneratio n was seen with IN-1 or with infusion of Dantrolene, an inhibitor of NI-35/ 250 activity in vitro. With infusion of nerve growth factor rostral to the nerve graft, 40% of the fibers at the rostral end of the graft were found a t 0.5 mm, 34% at 1 mm, 24% at 2 mm and 14% at 3 mm (the infusion site) into the spinal cord. Treatment with IN-1 antibodies did not enhance the growth -promoting effects of nerve growth factor. We suggest that the neurite growth inhibitors NI-35 or NI-250 do not play a major inhibitory role in the regeneration of the ascending sensory fibers across a nerve bridge and back into the spinal cord of the adult rat. (C) 2 000 IBRO. Published by Elsevier Science Ltd. All rights reserved.