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

M. Oudega, C. Rosano, D. Sadi, P. M. Wood, M. E. Schwab, T. Hagg

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Abstract

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 confirmed in tissue sections and cerebrospinal fluid, and its effectiveness demonstrated in co-cultures of oligodendrocytes and sensory neurons. With a two week infusion of control vehicle into the dorsal spinal cord 3mm rostral to the nerve graft, only 3±2% of the anterogradely labeled sensory fibers present at the rostral end of the nerve graft had grown up to 0.5mm, but not farther into the spinal cord. A similar limited extent of regeneration 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 at 0.5mm, 34% at 1mm, 24% at 2mm and 14% at 3mm (the infusion site) into the spinal cord. Treatment with IN-l 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. Copyright (C) 2000 IBRO.

Original languageEnglish (US)
Pages (from-to)873-883
Number of pages11
JournalNeuroscience
Volume100
Issue number4
DOIs
StatePublished - Oct 11 2000

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Keywords

  • Conditioning lesion
  • IN-1
  • Intraspinal implantation
  • Nerve growth factor
  • Neurotrophic factor
  • Peripheral nerve graft

ASJC Scopus subject areas

  • Neuroscience(all)

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