Neurotrophin potentiation of iron-induced spinal cord injury.

Previous studies have shown that pretreatment with neurotrophins can potentiate the vulnerability of cultured neurons to excitotoxic and free radical-induced necrosis, in contrast to their well known neuroprotective effects against apoptosis. Here we tested the hypothesis that this unexpected injury-potentiating effect of neurotrophins would also take place in the adult rat spinal cord. Fe(3+)-citrate was injected stereotaxically into spinal cord gray matter in adult rats in amounts sufficient to produce minimal tissue injury 24 h later. Twenty-four-hour pretreatment with brain-derived neurotrophic factor, neurotrophin-3, or neurotrophin-4/5, but not nerve growth factor, markedly enhanced tissue injury in the gray matter as evidenced by an increase in the damaged area, as well as the loss of neurons and oligodendrocytes. Consistent with maintained free radical mediation, the neurotrophin-potentiated iron-induced spinal cord damage was blocked by co-application of the antioxidant N-tert-butyl-(2-sulfophenyl)-nitrone. These data support the hypothesis that the overall neuroprotective properties of neurotrophins in models of acute injury to the spinal cord may be limited by an underlying potentiation of free radical-mediated necrosis.