Temporal effects of edaravone, a free radical scavenger, on transient ischemia-induced neuronal dysfunction in the rat hippocampus.
We examined the effect of a free radical scavenger edaravone on ischemia/reperfusion-induced impairment of long-term potentiation in the perforant path-dentate gyrus synapses of the rat hippocampus, as a measure of functional outcome 4 days after transient global ischemia (2-vessel occlusion, 10 min). Edaravone (3 and 10 mg/kg, i.v.) immediately after reperfusion (Day 0) alleviated ischemia-induced impairment of long-term potentiation in a dose-related manner, whereas treatment on Day 1 or 4 after reperfusion failed to rescue the impaired long-term potentiation. Edaravone administration on Day 0 also prevented the post-ischemic increase in hydroxyl radical formation and the expression of vascular endothelial growth factor, basic fibroblast growth factor and neuronal and inducible nitric oxide synthases of the hippocampus. Thus, edaravone protected the rat hippocampus from ischemia-induced long-term potentiation impairment with a therapeutic time window, suggesting that free radical formation after ischemia/reperfusion is a pivotal trigger of neurofunctional complications after global ischemic stroke.
Otani
Hiroshi
H
Department of Neuropharmacology, Hokkaido Graduate University School of Medicine, Sapporo 060-8638, Japan.
Togashi
Hiroko
H
Jesmin
Subrina
S
Sakuma
Ichiro
I
Yamaguchi
Taku
T
Matsumoto
Machiko
M
Kakehata
Hitoshi
H
Yoshioka
Mitsuhiro
M
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000503:physiopathology*; D000077553:Edaravone; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017665:Hydroxyl Radical / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D018613:Microscopy, Confocal; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D019580:Perforant Pathway / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D016166:Free Radical Scavengers; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D017665:Hydroxyl Radical; D019001:Nitric Oxide Synthase; D000077553:Edaravone; D000983:Antipyrine