Basic Fibroblast Growth Factor Protects against Hypoxia-Ischemia and NMDA Neurotoxicity in Neonatal Rats

Kazuhiko Nozaki, Seth P. Finklestein, M. Flint Beal
1993 Journal of Cerebral Blood Flow and Metabolism  
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 exam ined whether systemically administered bFGF could pre vent neuronal damage induced by either EAAs or hypox ia-ischemia in vivo. Neuroprotective effects were exam ined in a neonatal model of hypoxia-ischemia (unilateral ligation of the carotid artery followed by exposure to 8% oxygen for 1.5
more » ... 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 j-lg/kg) 30 min before intrastriatal injection of NMDA showed a dose-dependent neuroprotective effect. Re peated doses of bFGF (IOO j-lg/kg) both before and after Perinatal hypoxic-ischemia brain injury is a seri ous clinical problem with severe neurological con sequences such as cerebral palsy, mental and phys ical retardation, and seizures (Nelson and Ellen berg, 1986; Torfs et aI., 1990). Recent studies have implicated excitatory amino acids (EAAs) in the pathogenesis of neuronal injury in hypoxia ischemia, hypoglycemia, seizures, and some neuro degenerative diseases (Beal et aI.
doi:10.1038/jcbfm.1993.27 pmid:8436614 fatcat:4xcifid37zgvrl42jkjgmr6bwi