title: Normobaric hyperoxia and delayed tPA treatment in a rat embolic stroke model.
abstract: 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 spectrophotometric 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 approximately 30% and approximately 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 microL, 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.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Nils
authors.initials: N
authors.lastname: Henninger
authors.forename: Bernt T
authors.initials: BT
authors.lastname: Bratane
authors.forename: Birgul
authors.initials: B
authors.lastname: Bastan
authors.forename: James
authors.initials: J
authors.lastname: Bouley
authors.forename: Marc
authors.initials: M
authors.lastname: Fisher