UMMS Affiliation

Advanced MRI Center, Department of Radiology

Publication Date

2018-02-05

Document Type

Article

Disciplines

Nervous System Diseases | Neuroscience and Neurobiology | Radiology

Abstract

BACKGROUND: Positron emission tomography (PET) using translocator protein (TSPO) ligands has been used to detect neuroinflammatory processes in neurological disorders, including multiple sclerosis (MS). The aim of this study was to evaluate neuroinflammation in a mouse MS model (EAE) using TSPO-PET with (18)F-VC701, in combination with magnetic resonance imaging (MRI).

METHODS: MOG35-55/CFA and pertussis toxin protocol was used to induce EAE in C57BL/6 mice. Disease progression was monitored daily, whereas MRI evaluation was performed at 1, 2, and 4 weeks post-induction. Microglia activation was assessed in vivo by (18)F-VC701 PET at the time of maximum disease score and validated by radioligand ex vivo distribution and immunohistochemistry at 2 and 4 weeks post-immunization.

RESULTS: In vivo and ex vivo analyses show that (18)F-VC701 significantly accumulates within the central nervous system (CNS), particularly in the cortex, striatum, hippocampus, cerebellum, and cervical spinal cord of EAE compared to control mice, at 2 weeks post-immunization. MRI confirmed the presence of focal brain lesions at 2 weeks post-immunization in both T1-weighted and T2 images. Of note, MRI abnormalities attenuated in later post-immunization phase. Neuropathological analysis confirmed the presence of microglial activation in EAE mice, consistent with the in vivo increase of (18)F-VC701 uptake.

CONCLUSION: Increase of (18)F-VC701 uptake in EAE mice is strongly associated with the presence of microglia activation in the acute phase of the disease. The combined use of TSPO-PET and MRI provided complementary evidence on the ongoing disease process, thus representing an attractive new tool to investigate neuronal damage and neuroinflammation at preclinical levels.

Keywords

EAE monophasic model, MRI, Multiple sclerosis, Neuroinflammation, TSPO-PET

Rights and Permissions

© The Author(s). 2018. Open Access.This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

DOI of Published Version

10.1186/s12974-017-1044-x

Source

J Neuroinflammation. 2018 Feb 5;15(1):33. doi: 10.1186/s12974-017-1044-x. Link to article on publisher's site

Journal/Book/Conference Title

Journal of neuroinflammation

Related Resources

Link to Article in PubMed

PubMed ID

29402285

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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