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 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 micrograms/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 approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/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.
Kirschner
P B
PB
Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114, USA.
Henshaw
R
R
Weise
J
J
Trubetskoy
V
V
Finklestein
S
S
Schulz
J B
JB
Beal
M F
MF
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D018846:Excitatory Amino Acids / Q000633:toxicity*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D000860:Hypoxia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008314:Malonates / Q000633:toxicity; D016202:N-Methylaspartate / Q000633:toxicity; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018846:Excitatory Amino Acids; D008314:Malonates; D016222:Fibroblast Growth Factor 2; D016202:N-Methylaspartate; C030290:malonic acid; D015655:1-Methyl-4-phenylpyridinium