Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons dependon the temporal pattern of neurotrophin administration

This study shows that both BDNF and NT-3 can prevent cell death in axotomiz ed adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprot ection depends on the temporal pattern of treatment. At 8 weeks after cervi cal spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infus ion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy an d 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoi dal space with either BDNF or NT-3 gave similar survival rates, while a com bination of BDNF and NT-3 resulted in 96% survival, although the cells were atrophic. When administration of either BDNF or NT-3 was delayed and perfo rmed during postoperative weeks 5-8, the number of surviving neurons was in creased compared to early treatment. Delayed treatment with a combination o f BDNF and NT-3 resulted in complete survival and a reduction in neuronal a trophy. A decreased expression of TrkB receptors and microtubule-associated protein-2 in the RSNs after axotomy was counteracted by BDNF and NT-3. Mic roglial activity remained increased even when complete cell survival was ac hieved. Thus, the combination of neurotrophins as well as the temporal patt ern of treatment need to be adequately defined to optimize survival of inju red spinal tract neurons.