BDNF-MEDIATED RESCUE OF AXOTOMIZED MOTOR-NEURONS DECREASES WITH INCREASING DOSE

DIRECT application of brain-derived neurotrophic factor (BDNF) to the cut end of axotomized immature motor neurones had only transient survi val-promoting effects. Therefore, we have examined whether additional delivery of BDNF with repeated subcutaneous injections (1 mg/ml) could potentiate this short-term rescue of the lesioned sciatic and facial motor neurones in neonatal rats. Direct application of BDNF combined w ith intermittent (3-day intervals) injections slightly improved motor neurone survival. However, when BDNF was injected daily in addition to the direct application, the number of surviving lesioned motor neuron es was markedly reduced. These findings, corroborated by results in em bryonic spinal cord cultures, show that a dose-dependent reversal of B DNF-mediated positive effects on motor neurones occurs in vivo.