title: Early outcome and blood-brain barrier integrity after co-administered thrombolysis and hyperbaric oxygenation in experimental stroke.
abstract: BACKGROUND
  After promising results in experimental stroke, normobaric (NBO) or hyperbaric oxygenation (HBO) have recently been discussed as co-medication with tissue plasminogen activator (tPA) for improving outcome. This study assessed the interactions of hyperoxia and tPA, focusing on survival, early functional outcome and blood-brain barrier (BBB) integrity following experimental stroke.
  
  
  METHODS
  Rats (n = 109) underwent embolic middle cerebral artery occlusion or sham surgery. Animals were assigned to: Control, NBO (60-minute pure oxygen), HBO (60-minute pure oxygen at 2.4 absolute atmospheres), tPA, or HBO+tPA. Functional impairment was assessed at 4 and 24 hours using Menzies score, followed by intravenous application of FITC-albumin as a BBB permeability marker, which was allowed to circulate for 1 hour. Further, blood sampling was performed at 5 and 25 hours for MMP-2, MMP-9, TIMP-1 and TIMP-2 concentration.
  
  
  RESULTS
  Mortality rates did not differ significantly between groups, whereas functional improvement was found for NBO, tPA and HBO+tPA. NBO and HBO tended to stabilize BBB and to reduce MMP-2. tPA tended to increase BBB permeability with corresponding MMP and TIMP elevation. Co-administered HBO failed to attenuate these early deleterious effects, independent of functional improvement.
  
  
  CONCLUSIONS
  The long-term consequences of simultaneously applied tPA and both NBO and HBO need to be addressed by further studies to identify therapeutic potencies in acute stroke, and to avoid unfavorable courses following combined treatment.
authors.affiliation: Department of Neurology, University of Leipzig, Liebigstr, 20, 04103 Leipzig, Germany. dominik.michalski@medizin.uni-leipzig.de.
authors.forename: Dominik
authors.initials: D
authors.lastname: Michalski
authors.forename: Johann
authors.initials: J
authors.lastname: Pelz
authors.forename: Christopher
authors.initials: C
authors.lastname: Weise
authors.forename: Johannes
authors.initials: J
authors.lastname: Kacza
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.forename: Jens
authors.initials: J
authors.lastname: Grosche
authors.forename: Manja
authors.initials: M
authors.lastname: Kamprad
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schneider
authors.forename: Carsten
authors.initials: C
authors.lastname: Hobohm
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig