22. European Stroke Conference 5 Experimental studies A 15:10 - 15:20 Long Term Statin Therapy and the Development of Cerebral Microbleeds in Cerebral Amyloid Angiopathy – A Rodent in-vivo Approach A. Venus1, B. Reuter2, S. Grudzenski3, P. Heiler4, L.R. Schad5, M. Staufenbiel6, M.G. Henneri-ci7, M. Fatar8 Departement of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY1,Departement of Neurology, Universitätsmedizin Mannheim, Uni-versity of Heidelberg, Mannheim, GERMANY2, Departement of Neurology, Universitäts-medizin Mannheim, University of Heidelberg, Mannheim, GERMANY3, Computer Assisted Clinical Medicine, University of Heidelberg, Mannheim, GERMANY4, Computer Assisted Clinical Medicine, University of Heidelberg, Mannheim, GERMANY5, Neuroscience Discov-ery, Novartis Institutes for BioMedical Research, Basel, SWITZERLAND6, Departement of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMA-NY7, Departement of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, GERMANY8 Background: In cerebral amyloid angiopathy (CAA), the accumulation of amyloid beta (AB) in cortical and leptomeningeal vessels is the major cause of cerebral microbleeds (cMBs) and spontaneous lobar hemorrhage. Although CAA is increasingly recognized, today no specific therapy is available and experimental efforts are poor. Since statins are known to have bene-ficial effects in neurodegenerative disorders, we hypothesized that they might lower the pro-gression of CAA, too. Methods: We investigated the effect of long term atorvastatin treatment in a mouse model of CAA, the APP23-transgenic (tg) mouse line (n=42). Mice were fed with atorvastatin-supplemented food 60 mg/kg beginning at the age of 8 months (n=13), 12 months (n=7), and 16 months (n=6), respectively. A control group (n=16) was fed with standard food. At the age of 24 months 9.4 T magnetic resonance imaging including T2, T2* sequences (coro-nal plane, 18 slides) and time of flight MR-angiography (raw data 128 slides) was performed to assess the numbers of cMBs. Results: During atorvastatin treatment the APP23-tg mice group showed an average of 27.4±15.6 cMBs, compared to 35±18.5 in the untreated group (p=0.159) irrespective of time of treatment. After incorporation of a CAA-score with adjustment for cMB size (≤100 μm, 150-200 μm, >200 μm), differences between the atorvastatin treated group and controls still showed a trend towards smaller numbers in the treated vs. control groups, but failed to reach statistical significance (44±25.5 vs. 58±33.1, p=0.132). Conclusion: Probably due to the small number of animals studied, a high variability of cMBs in all treatment and con-trol groups, our results failed to show a significant reduction of progressive cMBs after long-term atorvastatin treatment in this CAA model. Yet, numbers of cMBs were not higher under long term atorvastatin therapy, which indicates safe usage of statins in CAA without increased cMB rates. Figure 1. Coronal sections of a domestic Figure 1. Coronal sections of a domestic pig brain one hour after injection of endothelin-1, cau-sing focal ischemia. (A) CTP-CBV and (B) CBF functional maps, (C) 18F-FDG PET images, (D) MR-ADC and (E) DWI maps, and (F) TTC-stained excised brain. All imaging and histo-logy were completed within 35 minutes. Within the infarcted tissue, outlined on TTC slices: 1) DWI-hyperintensities, and ADC-hypointensities are observed in all slices, 2) Uptake of FDG is increased and decreased in the periphery and core, respectively, 3) Normal or increased CBV and a decrease in CBF is observed. This CBF/CBV mismatch within infarcted tissue may be caused by the opening of arteriovenous shunts, representing acute non-nutritive hyperemia. 58 © 2013 S. Karger AG, Basel Scientific Programme
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