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

• Published in: Neuroscience 2000-01, Vol.100 (4), p.873-883
• Main Authors: Oudega, M, Rosano, C, Sadi, D, Wood, P.M, Schwab, M.E, Hagg, T
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - metabolism; Antibodies - pharmacology; Axons - metabolism; Axons - physiology; Binding, Competitive; Biological and medical sciences; Cell Transplantation; Cells, Cultured; Cerebral Cortex; conditioning lesion; Development. Senescence. Regeneration. Transplantation; Embryo, Mammalian; Female; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - metabolism; Hybridomas - cytology; Hybridomas - metabolism; Immunohistochemistry; IN-1; intraspinal implantation; Myelin Proteins - immunology; Myelin Proteins - metabolism; nerve growth factor; Nerve Growth Factor - pharmacology; Neurons, Afferent - metabolism; Neurons, Afferent - physiology; Neurons, Afferent - ultrastructure; neurotrophic factor; Nogo Proteins; Oligodendroglia - cytology; Oligodendroglia - metabolism; peripheral nerve graft; Peripheral Nerves - physiology; Peripheral Nerves - transplantation; Peripheral Nerves - ultrastructure; Rats; Rats, Sprague-Dawley; Regeneration; Spinal Cord - metabolism; Spinal Cord - physiology; Spinal Cord - surgery; Spinal Cord - ultrastructure; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(00)00350-X

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 3 mm 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 0.5 mm, 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 0.5 mm, 34% at 1 mm, 24% at 2 mm and 14% at 3 mm (the infusion site) into the spinal cord. Treatment with IN-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.