BASIC FIBROBLAST GROWTH-FACTOR PROTECTS AGAINST HYPOXIA-ISCHEMIA AND NMDA NEUROTOXICITY IN NEONATAL RATS

Basic fibroblast growth factor (bFGF) is a polypeptide that promotes neuronal survival and blocks excitatory amino acid (EAA) neurotoxicity in vitro at very low concentrations. In the present study, we examined whether systemically administered bFGF could prevent neuronal damage induced by either EAAs or hypoxia-ischemia in vivo. Neuroprotective effects were examined in a neonatal model of hypoxia-ischemia (unilateral ligation of the carotid artery followed by exposure to 8% oxygen for 1.5 h) and following intrastriatal injection of N-methyl-D-aspartate (NMDA) in 7-day-old rats. Intra-peritoneal administration of a single dose of bFGF (50-300 mug/kg) 30 min before intrastriatal injection of NMDA showed a dose-dependent neuroprotective effect. Repeated doses of bFGF (100 mug/kg) both before and after intrastriatal NMDA injection produced a much greater significant protective effect than a single dose administered prior to the injection. Intraperitoneal injection of single dose of 100 mug/kg of bFGF 30 min before hypoxia-ischemia reduced neuronal damage by 38% (p = 0.14), while administration of bFGF at a dose of 100 mug/kg i.p. three times, 30 min before and 0 and 30 min after hypoxia-ischemia. significantly reduced neuronal damage by 64% (p = 0.004). Systemic administration of bFGF did not change body temperature for up to 3 h. These results show that systemic administration of bFGF can exert neuroprotective effects against both NMDA-induced excitotoxicity and hypoxia-ischemia in vivo.