Page 57

Karger_ESC London_2013

London, United Kingdom 2013 4 Experimental studies A 15:00 - 15:10 DEFINING THE HYPER-ACUTE INFARCT CORE IN A PORCINE MODEL OF TRANSIENT CEREBRAL ISCHEMIA: A MULTI-MODAL IMAGING STUDY C.D. d’Esterre1, E. Fainardi2, S. Ceruti3, A. Saletti4, T.Y. Lee5 Western University, London, CANADA1,Neuroradiology Unit, Department of Neurosciences and Rehabilitation, AziendaOspedaliero-Universitaria, Ferrara, ITALY2, Neuroradiology Unit, Department of Neurosciences and Rehabilitation, AziendaOspedaliero-Universitaria, Ferr-ara, ITALY3, Neuroradiology Unit, Department of Neurosciences and Rehabilitation, Aziend-aOspedaliero- Universitaria, Ferrara, ITALY4, Lawson Health Research Institute, Robarts Re-search Institute, Western University, London, CANADA5 Background: CT perfusion (CTP)-derived parameters and MR-diffusion weighted imaging (DWI) are currently used to delineate infarct volume; however, reversibility of such defects has been demonstrated for both modalities. Methods: Twelve domestic pigs had a CTP scan prior to intracranial injection of endothe-lin- 1 (ET-1; 0.01mL/kg) into the left striatum. Subsequent CTP scans at 30min, 1hr, 1.5hrs were done to monitor ischemic progression. A second dose of ET-1 (0.01mL/kg) was inject-ed at 2hrs from the first injection. Twenty minutes after the second ET-1 injection, 18F-FDG was injected (300-380MBq). The animal was moved to a 1.5T MRI scanner where DWI was performed. The animal was then moved back to the CT scanner for a final CTP/PET acqui-sition within 10 minutes of the DWI. The brain was quickly removed and stained with tetra-zolium- chloride (TTC). The infarct volume defined by low intensity TTC stain, low CBF (< 9.3ml•min-1•100g-1), low CBV (< 1.07ml•100g-1), DWI hyper-intensity and low 18F-FDG uptake were determined. Linear regression was used to correlate the infarct volume measured by each imaging modality to that by the histological gold standard. Results: R2 values for CBF, CBV, DWI and FDG versus TTC-histology were 0.83, 0.69, 0.95 and 0.61, respectively. For the CBF and DWI parameters the slope of the fitted line was great-er than 1, while the slope of the fitted line for the CBV and CBFxCBV parameters was less than 1. Mean normalized (relative to the histologically defined infarct) values were 1.38, 0.82, 0.99, and 0.67 for CBF, CBV, DWI and FDG, respectively. Conclusion: The CTP-CBF and the imaging gold standard DWI both overestimated the TTC-infarct core in 66% and 58% of cases, while CTP-CBV, CBFxCBV and FDG-PET all underestimated the final infarct volume in 100% of animals. The CBF/CBV mismatch was observed within 4/12 DWI lesions, and 3/12 TTC defined infarcts (Figure 1). The CBF/CBV mismatch may not represent penumbra during the acute stroke setting. Table. Coefficients of determination (R2) and slopes of the regression lines for predicted infarct core, as defined by the four imaging parameters, versus TTC-defined true infarct. Also shown are normalized values (predicted infarct volume/true infarct volume) and the percent change between predicted and true infarct volumes. Cerebrovasc Dis 2013; 35 (suppl 3)1-854 57 3 Experimental studies A 14:50 - 15:00 Mechanisms of stem cell therapy in acute stroke. A putative role of mesenchymal stem cell secretions in regulation of ERK1/2 and AKT pathways. L. Tritschler1, S. Mirau-Weber2, E. Handwerker3, M.G. Hennerici4, S. Meairs5 UniversitätsMedizin Mannheim, Mannheim, GERMANY1,UniversitätsMedizin Mannheim, Mannheim, GERMANY2, UniversitätsMedizin Mannheim, Mannheim, GERMANY3, Univer-sitätsMedizin Mannheim, Mannheim, GERMANY4, UniversitätsMedizin Mannheim, Mann-heim, GERMANY5 Background: Although significant evidence suggests a beneficial role of mesenchymal stem cells (MSC) in acute ischemic stroke, the mechanisms of this action remain unclear. Both ERK1/2 and AKT pathways seem to be crucial. However, debate persists on whether these pathways are detrimental through promotion of inflammation and oxidative stress or beneficial through neuroprotection. Whether these pathways are affected by cell therapy is not known. We studied the effects of human MSC as well as their conditioned medium (MSC-CM) on ERK1/2 in acute ischemic stroke to elucidate mechanisms of stem cell therapy. Methods: 18 rats were allocated to 3 groups for permanent middle cerebral artery occlusion (MCAO). 3 hours after the onset of the occlusion, the animals received native medium, MSC (3.106 cells in 500 μl PBS), or MSC-CM (500 μl). 4 hours after the infusion, animals were sacrificed and the brains were quickly frozen. Protein extraction of non-affected and infarcted brain hemispheres was performed for western blot analysis. Results: As in previous reports, pERK1/2 and pAKT expression were increased in the infarcted hemisphere as compared to the non-affected hemisphere. MSC as well as MSC-CM treatments induced a decrease of the expression PERK1/2 and pAKT in the infarcted hemisphere. Expres-sion of beta-actin as a control protein was not affected either by the stroke or by the treatments. Values presented in the Table 1 are expressed as percentage of the protein level in the healthy side +/- sem. Conclusion: Our results demonstrate that MSC decrease elevated levels of both pAKT and pERK1/2 in MCAO. Moreover, the secretions of MSC are likely responsible for down regula-tion of AKT and ERK1/2, as MSC-CM has the same effect as MSC. Our study provides evi-dence for a target pathway of MSC therapy and suggests that administration of stem cell secre-tions in acute stroke could be just as effective as stem cells.


Karger_ESC London_2013
To see the actual publication please follow the link above