In a rat embolic stroke (eMCAO) model, the effects of 100% normobaric hyperoxia (NBO) with delayed recombinant tissue plasminogen activator (tPA) administration on ischemic lesion size and safety were assessed by diffusion- and perfusion (PWI)-weighted magnetic resonance imaging. NBO or room air (Air) by a face mask was started at 30 mins posteMCAO and continued for 3.5 h. Tissue plasminogen activator or saline was started at 3 h posteMCAO. Types and location of hemorrhagic transformation were assessed at 24 h and a spectrophotometry hemoglobin assay quantified hemorrhage volume at 10 h. In NBO-treated animals the apparent diffusion coefficient/PWI mismatch persisted during NBO treatment. Relative to Air groups, NBO treatment significantly reduced 24 h infarct volumes by ~30% and ~ 15% with or without delayed tPA, respectively ( P < 0.05). There were significantly more hemorrhagic infarction type 2 hemorrhages in Air/tPA versus Air/saline animals ( P < 0.05). Compared with Air/tPA, the combination of NBO with tPA did not increase hemorrhage volume at 10 h (4.0±2.4 versus 6.6±2.6 μL, P = 0.065) or occurrence of confluent petechial hemorrhages at 24 h ( P > 0.05), respectively. Our results suggest that early NBO treatment in combination with tPA at a later time point may represent a safe and effective strategy for acute stroke treatment.
Extension of the Therapeutic Window for Recombinant Tissue Plasminogen Activator With Argatroban in a Rat Model of Embolic Stroke
