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Neuroscience. 2019 Apr 1;403:136-144. doi: 10.1016/j.neuroscience.2017.12.014. Epub 2017 Dec 19.

Application of Europium-Doped Very Small Iron Oxide Nanoparticles to Visualize Neuroinflammation with MRI and Fluorescence Microscopy.

Author information

1
Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, 13353 Berlin, Germany; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Germany; Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
2
Department of Radiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
3
Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, 13353 Berlin, Germany; Cluster of Excellence NeuroCure and Department of Neurology and Experimental and Clinical Research Center, Universitätsmedizin Berlin, 10117 Berlin, Germany.
4
Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, 13353 Berlin, Germany.
5
Berlin Ultrahigh Field Facility, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
6
Institute for Medical Immunology, Charité-Universtitätsmedizin Berlin, 13353 Berlin, Germany; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Germany. Electronic address: carmen.infante@charite.de.

Abstract

Our recent studies demonstrated that electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) are promising MRI probes for detecting various pathological aspects of autoimmunity in the central nervous system (CNS). However, investigation of the precise tissue and cellular distribution of VSOP has been technically limited due to the need to use iron detection methods for VSOP visualization. Therefore, we assessed here the utility of europium (Eu)-doped VSOP as an MRI tool for in vivo investigations in the animal model experimental autoimmune encephalomyelitis (EAE), and as a tool to investigate histopathological processes in the CNS using fluorescence microscopy. We demonstrated that Eu-VSOP display the same properties as VSOP in terms of revealing inflammation-mediated changes by binding to brain endothelium in vitro, and in terms of visualizing brain lesions in EAE in vivo. MRI examinations with Eu-VSOP confirm that at peak disease particles accumulated inside the choroid plexus, and in cerebellar and meningeal lesions. Importantly, Eu-VSOP-based MRI showed for the first time in a longitudinal setup that particles were absent from the choroid plexus in mice during remission of EAE, but accumulated again during subsequent relapse. Within the choroid plexus, Eu-VSOP were associated both with monocytes/macrophages present in the plexus stroma, and associated with epithelial cells. Using Eu-VSOP, we demonstrated for the first time the involvement of the choroid plexus in relapses. Thus, Eu-VSOP have the potential to reveal various aspects of choroid plexus involvement in neuroinflammation, including monocyte recruitment from the blood and alterations of the choroid plexus epithelium.

KEYWORDS:

VSOP; europium; experimental autoimmune encephalomyelitis; iron oxide nanoparticles; magnetic resonance imaging; neuroinflammation

[Indexed for MEDLINE]

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