BASIC FGF, NGF, AND IGFS PROTECT HIPPOCAMPAL AND CORTICAL-NEURONS AGAINST IRON-INDUCED DEGENERATION

Iron is believed to contribute to the process of cell damage and death resulting from ischemic and traumatic insults by catalyzing the oxida tion of protein and lipids. Exposure of cultured rat hippocampal neuro ns to iron (FeSO4) caused a dose-dependent reduction in neuronal survi val, which was potentiated by ascorbate. Damage to neurons was associa ted with a significant level of oxygen radical in the culture medium. The iron chelator desferal prevented both the neuronal degeneration ca used by FeSO4 and the production of oxygen radical, demonstrating that ionic iron was responsible for the cell damage. Iron neurotoxicity wa s associated with an elevation of [Ca2+]i and was attenuated by NMDA r eceptor antagonists. Since recent findings demonstrated neuroprotectiv e effects of growth factors in cell culture and in vivo models of isch emia, we examined the effects of growth factors on iron-induced damage . Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), an d insulin-like growth factors (IGF-I and IGF-II) each protected neuron s against iron-induced damage. Both rat hippocampal and human cortical neurons were protected by these growth factors. Taken together, the d ata suggest that the neuroprotective effects of growth factors against excitotoxic/ischemic insults may result, in part, from a prevention o r attenuation of oxidative damage.