BASIC FIBROBLAST GROWTH-FACTOR PROTECTS AGAINST EXCITOTOXICITY AND CHEMICAL HYPOXIA IN BOTH NEONATAL AND ADULT-RATS

Basic fibroblast growth factor (bFGF) is a polypeptide growth factor t hat promotes neuronal survival. We recently found that systemic admini stration of bFGF protects against both excitotoxicity and hypoxia-isch emia in neonatal animals. In the present study, we examined whether sy stemically administered bFGF could prevent neuronal death induced by i ntrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypo xia induced by intrastriatal injection of malonate in adult rats and 1 -methyl-4-phenylpyridinium (MPP(+)) in neonatal rats. Systemic adminis tration of bFGF (100 mu g/kg) for three doses both before and after in trastriatal injection of either NMDA or malonate in adult rats produce d a significant neuroprotective effect. In neonatal rats, bFGF produce d dose-dependent significant neuroprotective effects against MPP(+) ne urotoxicity, with a maximal protection of similar to 50% seen with eit her a single dose of bFGF of 300 mu g/kg or three doses of 100 mu g/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 st rategy could be effective in stroke.