bFGF enhances the protective effects of MK-801 against ischemic neuronal injury in vitro.
The neuroprotective activity of basic fibroblast growth factor (bFGF) in combination with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation produced neuronal damage which was assessed using propidium iodide fluorescence. Treatment with increasing doses of bFGF demonstrated significant neuroprotection that was optimal at 10 ng ml-t. This effect was diminished at higher concentrations. MK-801, at the optimal concentration of 30 microM, demonstrated greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced the protection conferred by MK-801 alone. These results suggest that neurotrophic factors such as bFGF may augment the neuroprotective effects of NMDA antagonists against ischemic neuronal injury.
Barth
A
A
Department of Neurological Surgery, University of Washington, Harborview Medical Center, Seattle 98104-9766, USA.
Barth
L
L
Morrison
R S
RS
Newell
D W
DW
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000517:prevention & control*; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016222:Fibroblast Growth Factor 2; D016291:Dizocilpine Maleate