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Title: | Cuprizone-induced demyelination and demyelination-associated inflammation result in different proton magnetic resonance metabolite spectra | Authors: | Praet, Jelle Orije, Jasmien Kara, Firat Guglielmetti, Caroline SANTERMANS, Eva Daans, Jasmijn HENS, Niel Verhoye, Marleen Berneman, Zwi Ponsaerts, Peter Van der Linden, Annemie |
Issue Date: | 2015 | Publisher: | WILEY-BLACKWELL | Source: | NMR IN BIOMEDICINE, 28 (4), p. 505-513 | Abstract: | Conventional MRI is frequently used during the diagnosis of multiple sclerosis but provides only little additional pathological information. Proton MRS (H-1-MRS), however, provides biochemical information on the lesion pathology by visualization of a spectrum of metabolites. In this study we aimed to better understand the changes in metabolite concentrations following demyelination of the white matter. Therefore, we used the cuprizone model, a wellestablished mouse model to mimic type III human multiple sclerosis demyelinating lesions. First, we identified CX(3)CL1/CX(3)CR1 signaling as a major regulator of microglial activity in the cuprizone mouse model. Compared with control groups (heterozygous CX(3)CR1(+/-) C57BL/6 mice and wild type CX3CR1(+/+) C57BL/6 mice), microgliosis, astrogliosis, oligodendrocyte cell death and demyelination were shown to be highly reduced or absent in CX3CR1(-/-) C57BL/6 mice. Second, we show that 1H-MRS metabolite spectra are different when comparing cuprizone-treated CX3CR1(-/-) mice showing mild demyelination with cuprizone-treated CX3CR1(+/+) mice showing severe demyelination and demyelination-associated inflammation. Following cuprizone treatment, CX3CR1(+/+) mice show a decrease in the Glu, tCho and tNAA concentrations as well as an increased Tau concentration. In contrast, following cuprizone treatment CX3CR1(-/-) mice only showed a decrease in tCho and tNAA concentrations. Therefore, H-1-MRS might possibly allow us to discriminate demyelination from demyelination-associated inflammation via changes in Tau and Glu concentration. In addition, the observed decrease in tCho concentration in cuprizoneinduced demyelinating lesions should be further explored as a possible diagnostic tool for the early identification of human MS type III lesions. Copyright (C) 2015 John Wiley & Sons, Ltd. | Notes: | Correspondence to: Jelle Praet, Experimental Cell Transplantation Group, Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium. E-mail: jelle.praet@uantwerpen.be | Keywords: | CX3CR1; cuprizone; demyelination; spectroscopy; MRI;CX(3)CR1; cuprizone; demyelination; spectroscopy; MRI | Document URI: | http://hdl.handle.net/1942/18784 | ISSN: | 0952-3480 | e-ISSN: | 1099-1492 | DOI: | 10.1002/nbm.3277 | ISI #: | 000351474500009 | Rights: | © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2016 |
Appears in Collections: | Research publications |
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praet 1.pdf | Published version | 1.57 MB | Adobe PDF | View/Open |
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