Fibroblast growth factor-8 protects cultured rat hippocampal neurons from oxidative insult

Basic fibroblast growth factor (bFGF) has been reported to have neuroprotec tive properties following excitotoxic, metabolic, and oxidative insults. We report here that another FGF family member, FGF-8 is able to protect rat h ippocampal cultures from oxidative stress. The b isoform of FGF-8 protected hippocampal cultures from hydrogen peroxide with an EC50 of approximately 25 ng/ml. In a time course study, using pre-, co-, post-treatment paradigms , we report that bFGF and FGF-8b were neuroprotective when added as a pre-t reatment, co-treatment, and even at 2 h post-insult. Using neuronal enriche d cultures, we demonstrate that bFGF and FGF-8b neuroprotection partially r esults from a direct action of the growth factors on neurons. The direct ac tion on neurons may work in concert with normal and FGF-stimulated glial se cretion products to give the full FGF protective effect. FGF-8b showed maxi mal protection at 50 ng/ml, whereas bFGF showed maximal protection at 10 ng /ml. Despite requiring higher concentrations to elicit protection, FGF-8b i s able to attain levels of protection equivalent to that of bFGF (attenuati on of 75-80% of hydrogen peroxide induced death). We also report that bFGF and FGF-8b are able to protect the human neuroblastoma cell line, SK-N-MC, from peroxide-induced LDH release by 50%. From these studies, we conclude t hat FGF-sb is another member of the FGF family which may show in vivo effic acy for the treatment of oxidative insults, such as stroke. (C) 1999 Publis hed by Elsevier Science B.V. All rights reserved.