Increased corticofugal plasticity after unilateral cortical lesions combined with neutralization of the IN-1 antigen in adult rats

If damage to the central nervous system (CNS) occurs early in life, extensi ve rearrangements of the remaining fiber systems as well as regeneration of lesioned fibers take place. In the rat or hamster, newly grown projections have been described only if the lesion occurred within the first two weeks postnatally. This decreasing growth ability correlates with CNS maturation and the progression of myelination. Myelin contains the potent neurite gro wth inhibitors NI-35/250 that are crucially involved in the failure of long -distance regeneration and the lack of compensatory structural plasticity a fter adult CNS lesions. In this study, we show that extensive remodeling oc curs well after the termination of the growth permissive period in the adul t rat if we neutralize the inhibitory properties of myelin with the monoclo nal antibody IN-1. After ablation of one motor cortex and treatment with th e antibody IN-1, we observed that the remaining corticospinal tract (CST) f rom the spared hemisphere sprouted into the denervated, contralateral red n ucleus and pens. In the pens, these fibers terminated in a typical somatoto pic pattern. For comparison with neonatal plasticity, we performed the same lesion in two-day-old rats (no antibody). This lesion led as well to sprou ting of the remaining CST into denervated brainstem nuclei, resulting in a bilateral corticofugal projection. Our results show that neutralization of myelin-associated neurite-growth inhibitors after CNS lesions leads to a st ructural remodeling of the spared corticofugal fibers in adult rats, a proc ess normally restricted to a short postnatal period. (C) 1999 Wiley-Liss. I nc.