Combination effects of normobaric hyperoxia and edaravone on focal cerebral ischemia-induced neuronal damage in mice

Neurosci Lett. 2008 Aug 22;441(2):224-8. doi: 10.1016/j.neulet.2008.06.033. Epub 2008 Jun 18.


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.

MeSH terms

  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / therapeutic use
  • Blood Pressure / drug effects
  • Cell Death / drug effects
  • Cerebral Infarction / etiology
  • Cerebral Infarction / pathology*
  • Cerebral Infarction / therapy*
  • Disease Models, Animal
  • Edaravone
  • Free Radical Scavengers / therapeutic use*
  • Hyperbaric Oxygenation / methods*
  • In Situ Nick-End Labeling / methods
  • Infarction, Middle Cerebral Artery / complications
  • Male
  • Mice
  • Neurologic Examination
  • Neurons / drug effects
  • Neurons / pathology*
  • Tetrazolium Salts


  • Free Radical Scavengers
  • Tetrazolium Salts
  • triphenyltetrazolium
  • Edaravone
  • Antipyrine