Concurrent 11

not to be published. Concurrent 1 – Platform Session Wednesday, 13 August 2008: 1430–1445 h CEREBRAL INFARCT SIZE IS GENDER-DEPENDANT FOLLOWING TRANSIENT BUT NOT PERMANENT MIDDLE CEREBRAL ARTERY OCCLUSION IN MICE: DIFFERENTIAL EFFECTS ON NOX1, NOX2 AND NOX4 EXPRESSION CG Sobey, VH Brait, KA Jackman, AE Mast, TM DeSilva, AA Miller, GR Drummond Department of Pharmacology, Monash University, Melbourne, VIC Females are strongly protected against cerebral ischemia-reperfusion (I-R) damage but the underlying mechanisms are poorly understood. Moreover, it is not clear whether females are similarly protected during ischemia with no reperfusion (I-NR). Here we have tested whether females are protected to a similar degree during both cerebral I-R and I-NR, and whether the outcomes are associated with changes in expression of NADPH oxidase Nox subunits in the ischemic brain. Stroke was induced by 0.5 h middle cerebral artery occlusion in 6–8 week-old female and male C57Bl6J mice. After 24 h, brain infarct volume was measured in thionin-stained coronal sections. After I-R, males had a larger infarct volume than females (55 ± 11 vs 24 ± 6 mm; P < 0.05), whereas there was no gender difference following I-NR (88 ± 11 vs 88 ± 9 mm). After I-R in males, expression of Nox2 increased by ∼30% and Nox4 decreased by ∼20%, whereas in females neither isoform was altered by I-R. After I-NR in males, changes in Nox2 and Nox4 were slightly more pronounced than after I-R (+60% and −25%, respectively). However in females, in contrast to the lack of effects on brain Nox2 and Nox4 expression after I-R, marked changes occurred after I-NR (+70% and −40%, respectively). There were no differences in Nox1 expression between any of the groups. Thus, cerebral infarct size is gender-dependent following I-R but not I-NR in mice. The lack of protection in females after I-NR is associated with changes in brain expression of Nox2 and/or Nox4 not present after I-R. Concurrent 1 – Platform Session Wednesday, 13 August 2008: 1445–1500 h OPTIMIZING MISMATCH DEFINITIONS IN ACUTE STROKE MRI – AN EPITHET POST HOC STUDY Soren Christensen, Mark W Parsons, Deidre A De Silva, Martin Ebinger, Ken Butcher, John Fink, Patricia Desmond, P Alan Barber, C Bladin, C Levi, Geoffrey A Donnan, Stephen M Davis Royal Melbourne Hospital, University of Melbourne, VIC Background: The recently published EPITHET trial tested whether tissue plasminogen activator (tPA) attenuated growth in patients with a perfusion/diffusion weighted imaging mismatch, believed to identify potential treatment responders.The trial was negative for the primary growth outcome measure. Secondary outcome measures consistently showed a tendency for improved outcomes in the tPA group. Aims: Eighty-six percent of patients had mismatch, and we hypothesized that a more restrictive mismatch definition would identify an enriched population with larger treatment response. In this descriptive post-hoc analysis we investigated the effect of changing the Tmax and mismatch ratio definitions in order to identify effect sizes, definitions and outcome measures for use in future studies. Methods: Mismatch definitions were varied to identify subpopulations with mismatch frequencies from 10 to 100%. We recorded effect and significance level of the differences between treatment arms at each definition. Outcome measures were infarct growth and mRS 0–1. Results: More restrictive mismatch definitions were significantly correlated with larger growth differences between treatment arms R = 0.40 (P < 0.001) and identified a population with higher treatment response. The odds ratio for mRS 0–1 in the tPA arm showed a much weaker correlation R = 0.09 (P < 0.001) with mismatch definitions and although there was a constant trend for benefit of tPA, the group differences were not significant at any relevant threshold. Conclusion: More restrictive mismatch definitions identify subgroups of patients in EPITHET with higher and significant response to treatment. Based on EPITHET 360 patients are required to demonstrate effect on clinical outcomes.