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 × 102/mm2 (n = 5) vs. vehicle: 18.9 ± 2.4 × 102/mm2 (n = 5), P < 0.01] and subcortex [11.6 ± 1.5 × 102/mm2 (n = 5) vs. vehicle: 22.5 ± 2.1 × 102/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.