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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/18784

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
Citation: 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
URI: http://hdl.handle.net/1942/18784
DOI: 10.1002/nbm.3277
ISI #: 000351474500009
ISSN: 0952-3480
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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