Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors

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Abstract
After lesions in the differentiated central nervous system (CNS) of higher vertebrates, interrupted fibre tracts do not regrow and elongate by more than an initial sprout of approximately 1 mm. Transplantations of pieces of peripheral nerves into various parts of the CNS demonstrate the widespread capability of CNS neurons to regenerate lesioned axons over long distances in a peripheral nerve environment. CNS white matter, cultured oligodendrocytes (the myelin-producing cells of the CNS), and CNS myelin itself, are strong inhibitors of neuron growth in culture, a property associated with defined myelin membrane proteins of relative molecular mass (Mr) 35,000 (NI-35) and 250,000 (NI-250). We have now intracerebrally applied the monoclonal antibody IN-1, which neutralizes the inhibitory effect of both these proteins, to young rats by implanting antibody-producing tumours. In 2-6-week-old rats we made complete transections of the cortico-spinal tract, a major fibre tract of the spinal cord, the axons of which originate in the motor and sensory neocortex. Previous studies have shown a complete absence of cortico-spinal tract regeneration after the first postnatal week in rats, and in adult hamsters and cats. In IN-1-treated rats, massive sprouting occurred at the lesion site, and fine axons and fascicles could be observed up to 7-11 mm caudal to the lesion within 2-3 weeks. In control rats, a similar sprouting reaction occurred, but the maximal distance of elongation rarely exceeded 1 mm. These results demonstrate the capacity for CNS axons to regenerate and elongate within differentiated CNS tissue after the neutralization of myelin-associated neurite growth inhibitors.