Published Online
on November 22, 2006

A more recent version of this article appeared on January 1, 2007

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Submitted on April 18, 2006
Revised on August 25, 2006
Accepted on August 30, 2006

MRI Monitoring of Neuroinflammation in Mouse Focal Ischemia

Marlène Wiart PhD^*; Nathalie Davoust PhD; Jean-Baptiste Pialat MD; Virginie Desestret MD; Samir Moucharaffie MD; Tae-Hee Cho MD; Mireille Mutin BSc; Jean-Baptiste Langlois BSc; Olivier Beuf PhD; Jérôme Honnorat MD, PhD; Norbert Nighoghossian MD, PhD; and Yves Berthezène MD, PhD

From Université de Lyon, Lyon, F-69003, France; INSA de Lyon, Villeurbanne, F-69621, France; CNRS, UMR 5515, Bron, F-69677, France; Inserm, U630, Bron, F-69677; France (M.W., J.-B.P., S.M., T.-H.C., N.N., Y.B.); Université de Lyon, Lyon, F-69003, France; Experimental Neurobiology and Physiopathology, Inserm U433, University of Lyon, Faculté Laennec, Lyon, France (N.D., V.D., M.M., J.H.); Animage (J.-B.L.), Small Animal Multimodal Imaging Facility, Bat CERMEP, Bron cedex, France; and Université de Lyon, Lyon, F-69003, France; Laboratoire de RMN-Méthodologie & Instrumentation en Biophysique, UMR CNRS 5012, UCBL-ESCPE, Bat CPE, Villeurbanne cedex, France (O.B.).

^* To whom correspondence should be addressed. E-mail: wiart{at}creatis.insa-lyon.fr.

Background and Purpose--A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice.

Methods--Ultrasmall superparamagnetic particles of iron oxide (USPIO) were intravenously injected after permanent middle cerebral artery occlusion and monitored by high resolution MRI for 72 hours.

Results--We here present the first MRI data showing in vivo phagocyte-labeling obtained in mice with focal cerebral ischemia. USPIO-enhanced MRI kinetic analysis disclosed an inflammatory response surrounding the ischemic lesion and in the contralateral hemisphere via the corpus callosum. The imaging data collected during the first 36 hours postinjury suggested a spread of USPIO-related signal from ipsi- to contralateral hemisphere. Imaging data correlated with histochemical analysis showing inflammation remote from the lesion and ingestion of nanoparticles by microglia/macrophages.

Conclusions--The present study shows that MR-tracking of phagocyte cells is feasible in mice, which may have critical therapeutic implications given the potential neurotoxicity of activated microglia/macrophages in central nervous system disorders.

Key words: animal model • focal ischemia • inflammation • magnetic resonance imaging • ultrasmall superparamagnetic particles of iron oxide

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