Suchergebnisse

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. ; This work was supported by research grants G.0136.11 and G.0130.11 (granted to ZB, AVdL and PP) of the Fund for Scientific Research - Flanders (FWO - Vlaanderen, Belgium) and in addition by an "FWO - Krediet aan Navorsers" grant of the Fund for Scientific Research - Flanders (FWO -Vlaanderen, Belgium, granted to MV); next, by a Methusalem research grant from the Flemish government (granted to ZB) and in part by funding received from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement 278850 (INMiND) (granted to AVdL). Caroline Guglielmetti is holder of an IWT PhD grant (Institute for the Promotion of Innovation through Science and Technology in Flanders, IWT - Vlaanderen). Firat Kara is holder of an "FWO - Postdoc" grant of the Fund for Scientific Research - Flanders (FWO - Vlaanderen, Belgium). MRI equipment was funded by the Flemish Impulse funding for heavy scientific equipment (granted to AVdL).