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248 Scientific Programme 22. European Stroke Conference © 2013 S. Karger AG, Basel 4 Experimental studies The effects of different doses of bone marrow-derived mononuclear cells for acute ischemic stroke in spontaneously hypertensive rats A. Schmidt1, K. Diederich2, J.K. Strecker3, W.R. Schäbitz4, J. Minnerup5 Department of Neurology, University of Münster, Münster, GERMANY1, Department of Neu-rology, University of Münster, Münster, GERMANY2, Department of Neurology, University of Münster, Münster, GERMANY3, Department of Neurology, EVK Bielefeld, Bethel, Münster, GER-MANY4, Department of Neurology, University of Münster, Münster, GERMANY5 Introduction: Several studies have shown beneficial effects of bone marrow-derived mononuclear cells (BM-MNCs) in animal models of stroke. However, although the Stroke Therapy Academ-ic Industry Roundtable (STAIR) and the Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) emphasize the importance of pre-clinical dose-response studies and studies in animals with comorbidities before moving to clinical trials, these two issues have not been thoroughly addressed so far. Methods: Spontaneously hypertensive adult male rats were subjected to 60 min of middle cerebral artery occlusion (MCAO). Three hours after the onset of MCAO, animals received either placebo (n=19), or 1 million BM-MNCs/rat (n=18), or 5 million BM-MNCs/rat (n=20), or 20 million BM-MNCs/ rat (n=20) intravenously. Menzie’s neuroscore, the adhesive tape removal test, the cylinder test and the rotarod test were used to assess the functional outcome. Histological analyses were per-formed to determine the infarct volume and to investigate inflammatory processes. Results: Behavioral testing until day 3 after MCAO did not reveal significant differences between the four groups (neuroscore, P=0.980; rotarod test, P=0.670; adhesive tape removal test, P=0.922; cylinder test, P=0.350). Three days after MCAO, the infarct volumes were similar among the four groups (P = 0.595), and there were no differences in the cellular inflammatory processes. There was no dose-response relationship of treatment. Conclusion: Our study does not show beneficial effects of BM-MNCs for the treatment of acute ischemic stroke in spontaneously hypertensive rats, and it does not show a dose-response relation-ship, either. Further studies are necessary to evaluate the efficacy of BM-MNCs, when treatment is initiated later. Figure 1A. CT perfusion studies at admission, 24 hours, 7 days, and 3 months post ictus for AIS pa-tient 3, with confirmed recanalization at 24 hours. NCCT, CBV and CBF maps are shown in rows 1, 2 and 3, respectively. Here, a matched decrease in CBF and CBV is apparent at onset within the hypodense region on the NCCT. After recanalization, hyperperfusion and hypervolemia are seen at 24 hours and 7 days post stroke onset, the so-called “luxury perfusion syndrome”. This non-nutritive hypervolemic/hyperperfusion response was associated with only a short-term decline in clinical out-come. When examining all patients at 24 hours, 7 days and 3 months, an increase in CBV was pres-ent in 33%, 40% and 0% of patients, respectively, which was not associated with an average overall worsening of the NIHSS at any time point, compared to the patients without hypervolemia at onset. Figure 1B. CT perfusion studies at admission, 24 hours, 7 days, and 3 months post ictus for AIS pa-tient 29, with confirmed recanalization at 24 hours. NCCT, CBV and CBF maps are shown in rows 1, 2 and 3, respectively. Here, we show a patient with a CBF/CBV mismatch at admission with little evidence of early ischemic change on the corresponding NCCT. Even with confirmed recanalization/ reperfusion at 24 hours, portions of the supposedly viable (penumbra), hypervolemic tissue at ad-mission still progressed to infarction. For patients who recanalized, 31% (10/32) of patients had hy-pervolemic tissue at admission (the CBF/CBV mismatch) and 24 hours (either a matched increase, or mismatch in CBF/CBV), that went on to infarction.


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