BDNF abolishes the survival effect of NT-3 in axotomized clarke neurons ofadult rats

Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) have pre viously been shown to support survival and axonal regeneration in various t ypes of neurons. Also, synergistic neuroprotective effects of these neurotr ophins have been reported in descending rubrospinal neurons after cervical spinal cord injury (Novikova et al., [2000] Eur. J. Neurosci. 12:776-780). The present study investigates the effects of intrathecally delivered NT-3 and BDNF on the survival and atrophy of ascending spinocerebellar neurons o f Clarke nucleus (CN) after cervical spinal cord injury in adult rats. At 8 weeks after cervical spinal cord hemisection, 40% of the axotomized CN neu rons had been lost, and the remaining cells exhibited marked atrophy. Micro glial activity was significantly increased in CN of the operated side. Intr athecal infusion of NT-3 for 8 weeks postoperatively resulted in 91% cell s urvival and a reduction in cell atrophy, but did not reduce microglial acti vity. In spite of the fact that the CN neurons expressed both TrkC and TrkB receptors, only NT-3 had a neuroprotective effect, whereas BDNF was ineffe ctive. Furthermore, when a combination of BDNF and NT-3 was administered, t he neuroprotective effect of NT-3 was lost. The present results indicate a therapeutic potential for NT-3 in the treatment of spinal cord injury, but also demonstrate that in certain neuronal populations the neuroprotection o btained by a combination of neurotrophic factors may be less than that of a single neurotrophin. J. Comp. Neurol. 428:671-680, 2000. (C) 2000 Wiley-Li ss, Inc.