NEUROTROPHIN-3 AND BRAIN-DERIVED NEUROTROPHIC FACTOR INDUCE OLIGODENDROCYTE PROLIFERATION AND MYELINATION OF REGENERATING AXONS IN THE CONTUSED ADULT-RAT SPINAL-CORD

Functional loss after spinal cord injury (SCI) is caused, in part, by demyelination of axons surviving the trauma. Neurotrophins have been s hown to induce oligodendrogliagenesis in vitro, but stimulation of oli godendrocyte proliferation and myelination by these factors in vivo ha s not been examined. We sought to determine whether neurotrophins can induce the formation of new oligodendrocytes and myelination of regene rating axons after SCI in adult rats. In this study, fibroblasts produ cing neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor, nerve growth factor, basic fibroblast gro wth factor, or P-galactosidase (control grafts) were transplanted suba cutely into the contused adult rat spinal cord. At 10 weeks after inju ry, all transplants contained axons. NT-3 and BDNF grafts, however, co ntained significantly more axons than control or other growth factor-p roducing grafts. In addition, significantly more myelin basic protein- positive profiles were detected in NT-3 and BDNF transplants, suggesti ng enhanced myelination of ingrowing axons within these neurotrophin-p roducing grafts. To determine whether augmented myelinogenesis was ass ociated with increased proliferation of oligodendrocyte lineage cells, bromodeoxyuridine (BrdU) was used to label dividing cells. NT-3 and B DNF grafts contained significantly more BrdU-positive oligodendrocytes than controls. The association of these new oligodendrocytes with ing rowing myelinated axons suggests that NT-3- and BDNF-induced myelinoge nesis resulted, at least in part, from expansion of oligodendrocyte li neage cells, most likely the endogenous oligodendrocyte progenitors. T hese findings may have significant implications for chronic demyelinat ing diseases or CNS injuries.