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% O-2, 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 +/- 63 mm(3) (n = 10) vs. vehicle: 65.5 +/- 5.9 mm(3) (n = 14) P<0.05], but not in the two monotherapy-groups [NBO: 50.5 +/- 5.8 mm(3) (n = 14) and edaravone: 56.7 +/- 5.8 mm(3) (n = 10)]. The combination therapy reduced TUNEL-positive cells in the ischemic boundary zone both in cortex [6.0 +/- 1.4 x 10(2)/mm(2) (n = 5) vs. vehicle: 18.9 +/- 2.4 x 10(2)/mm(2) (n 5), P<0.01] and subcortex [11.6 +/- 1.5 x 10(2)/mm(2) (n = 5) vs. vehicle: 22.5 +/- 2.1 x 10(2)/mm(2) (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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.