Cerebral blood flow and glucose metabolism in ischemic stroke : multimodal imaging investigations in a clinically relevant rat model

摘要: Ischemic stroke is one of the leading causes death worldwide. also a major cause long-term disability with vast socioeconomic results for patients, their relatives and health services. Over last decades, experimental research has resulted in significant progress our understanding mechanisms to brain injury after ischemic stroke. However, so far, translational targeting these failed. This failure general consensus that more integrative approach needed account not only neurobiology under ischemia, but impact on neurovascular interface. Accordingly, new tools simultaneously imaging perturbing this interface needs be established. The aims present work were firstly develop an model rats closely mimics human Secondly, goal was incorporate perfusionand metabolic using high-field magnetic resonance (HF-MRI) positron emission tomography (PET). Finally we wanted apply treatment study interface, use HF-MRI PET assess outcome. We translated endovascular techniques from bedside bench interest realizing rat focal cerebral which microwire navigated X-ray fluoroscopy occluding position middle artery (MCA). Furthermore, able technique facilitate intra-arterial microcatheter access cerebrovascular system accommodating injections varying degree selectivity. Next, established protocols obtain pathophysiological events following acute subacute applied aforementioned vascular endothelial growth factor B (VEGF-B) found translation clinical setting opened up several possibilities perturb In comparison earlier models rat, presented Paper I produces pathophysiology resembling showed highly compatible small animal systems possibility occlude MCA inject substances directly supply before, during (Paper II). makes it possible control blood flow scanning various modalities. [2-F]2-Fluoro-2-deoxy-D-glucose investigations ischemia III provided evidence hypermetabolism glucose occurring parallel diffusion restriction water, suggesting extension current paradigm behind infarct-related water. IV, VEGF-B antagonism result reduction volume, indicating mechanism action warranting further studies LIST OF SCIENTIFIC PAPERS thesis based papers: I. Arnberg F, Lundberg J, Soderman M, Damberg P Holmin S. Imageguided method inducing cortical or striatal infarction controlling MRI. Stroke (2012). II. Samen E, Lu L, Grafstrom StoneElander S Selective administration 18F-FDG effects hemispheric uptake. Neuroradiology (2014) III. Nikkhou-Aski S, Little P, Mitsios N, Mulder Stone-Elander Imaging clinically relevant model: revisited. (2015) IV. Fredriksson Nilsson I, Eriksson U, VEGFB reduces infarct size Manuscript. Scientific papers by author are part thesis: Lindh C, Wennersten A, Mathiesen T. Differences cell between high low energy adult rats. Acta Neurochirurgica (2008). Zu Winberg Palmer G, Svensson P-J, Wester T Agneta Nordenskjold. Mutation analysis motor neuron pancreas homeobox 1 (MNX1, former HLXB9) gene Swedish patients Currarino syndrome. Journal Pediatric Surgery (2011). I-L, Zedenius J Sundin A. Thyroid incidentaloma detected fluorodeoxyglucose tomography/computed tomography: practical management algorithm. World Gahm L-N-iminoethyl-lysine trauma attenuates cellular proliferation astrocyte differentiation. V. Olofsson MH, Tegnebratt T, Thorell JO, Metabolism epidermal receptor probe [11C]PD153035: biodistribution tumor uptake Nuclear Medicine (2013). VI. Majeed Meijer K, Larrazabal R, Luijckx GJ, Roberts RS Schulman Mortality vitamin K antagonist-related intracerebral bleeding treated plasma 4-factor prothrombin complex concentrate. Thrombosis Haemostasis (2014). VII. Kenne Jaff Muller Nava Kaipe H, Ringden, O Superselective umbilical cord BM animals. Bone Marrow Transplantation VIII. Toth Haggkvist Halldin Gulyas Acute neuroinflammation rat: longitudinal immunofluorescent tracking. Brain Structure Function (2015). IX. Olsson Jussing Dahlen Axelsson Ringden O, H Intra-arterial placenta-derived decidual stromal cells superior mesenteric rabbit: distribution cells, feasibility safety Cell