title: Fibroblast growth factor-8 protects cultured rat hippocampal neurons from oxidative insult.
abstract: Basic fibroblast growth factor (bFGF) has been reported to have neuroprotective properties following excitotoxic, metabolic, and oxidative insults. We report here that another FGF family member, FGF-8 is able to protect rat hippocampal 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-treatment, co-treatment, and even at 2 h post-insult. Using neuronal enriched cultures, we demonstrate that bFGF and FGF-8b neuroprotection partially results from a direct action of the growth factors on neurons. The direct action on neurons may work in concert with normal and FGF-stimulated glial secretion products to give the full FGF protective effect. FGF-8b showed maximal protection at 50 ng/ml, whereas bFGF showed maximal protection at 10 ng/ml. Despite requiring higher concentrations to elicit protection, FGF-8b is able to attain levels of protection equivalent to that of bFGF (attenuation 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 that FGF-8b is another member of the FGF family which may show in vivo efficacy for the treatment of oxidative insults, such as stroke.
authors.affiliation: Eli Lilly and Company, Neuroscience Research Division, Indianapolis, IN 46285, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Mark
authors.forename: K S
authors.initials: KS
authors.lastname: Fuson
authors.forename: K
authors.initials: K
authors.lastname: Keane-Lazar
authors.forename: P C
authors.initials: PC
authors.lastname: May
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: C496456:FGF8 protein, human; C496458:Fgf8 protein, rat; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors