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 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.
Oudega
M
M
The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33136, USA. moudega@miamiproj.med.miami.edu
Rosano
C
C
Sadi
D
D
Wood
P M
PM
Schwab
M E
ME
Hagg
T
T
D000818:Animals; D000906:Antibodies / Q000378:metabolism* / Q000494:pharmacology; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001667:Binding, Competitive; D017690:Cell Transplantation; D002478:Cells, Cultured; D002540:Cerebral Cortex; D004622:Embryo, Mammalian; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006825:Hybridomas / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D009185:Myelin Proteins / Q000276:immunology / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010525:Peripheral Nerves / Q000502:physiology / Q000637:transplantation / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology* / Q000601:surgery / Q000648:ultrastructure
D000906:Antibodies; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D020932:Nerve Growth Factor