Basic Fibroblast Growth Factor Protects against Excitotoxicity and Chemical Hypoxia in Both Neonatal and Adult Rats

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Abstract
Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia–ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-d-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 μg/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of ∼50% seen with either a single dose of bFGF of 300 μg/kg or three doses of 100 μg/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood–brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.