Combination effects of normobaric hyperoxia and edaravone on focal cerebral ischemia-induced neuronal damage in mice.
We evaluated the potential neuroprotective effects of combination treatment with normobaric hyperoxia (NBO) and edaravone, a potent scavenger of hydroxyl radicals, on acute brain injuries after stroke. Mice subjected to 2-h filamental middle cerebral artery occlusion were treated with NBO (95% O2, during the ischemia) alone, with edaravone (1.5 mg/kg, intravenously after the ischemia) alone, with both of these treatments (combination), or with vehicle. The histological and neurological score were assessed at 22-h after reperfusion. Infarct volume was significantly reduced in the combination group [36.3+/-6.7 mm3 (n=10) vs. vehicle: 65.5+/-5.9 mm3 (n=14) P<0.05], but not in the two monotherapy-groups [NBO: 50.5+/-5.8 mm3 (n=14) and edaravone: 56.7+/-5.8 mm3 (n=10)]. The combination therapy reduced TUNEL-positive cells in the ischemic boundary zone both in cortex [6.0+/-1.4 x 10(2)/mm2 (n=5) vs. vehicle: 18.9+/-2.4 x 10(2)/mm2 (n=5), P<0.01] and subcortex [11.6+/-1.5 x 10(2)/mm2 (n=5) vs. vehicle: 22.5+/-2.1 x 10(2)/mm2 (n=5), P<0.01]. NBO and combination groups exhibited significantly reduced neurological deficit scores at 22-h after reperfusion (vs. vehicle, P<0.05). Combination therapy with NBO plus edaravone prevented the neuronal damage after focal cerebral ischemia and reperfusion in mice, compared with monotherapy of NBO or edaravone.
Nonaka
Yuko
Y
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Shimazawa
Masamitsu
M
Yoshimura
Shinichi
S
Iwama
Toru
T
Hara
Hideaki
H
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology* / Q000628:therapy*; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006931:Hyperbaric Oxygenation / Q000379:methods*; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D051379:Mice; D009460:Neurologic Examination; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D013778:Tetrazolium Salts
D016166:Free Radical Scavengers; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D000077553:Edaravone; D000983:Antipyrine