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Magnetic resonance imaging characterization of different experimental autoimmune encephalomyelitis models and the therapeutic effect of glatiramer acetate

Aharoni, Rina, Sasson, Efrat, Blumenfeld-Katzir, Tamar, Eilam, Raya, Sela, Michael, Assaf, Yaniv and Arnon, Ruth 2013. Magnetic resonance imaging characterization of different experimental autoimmune encephalomyelitis models and the therapeutic effect of glatiramer acetate. Experimental Neurology 240 , pp. 130-144. 10.1016/j.expneurol.2012.11.004

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Abstract

The roles of inflammation and degeneration as well as of gray matter abnormalities in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are controversial. We analyzed the pathological manifestations in two EAE models, the chronic oligodendrocyte glycoprotein (MOG)-induced versus the relapsing–remitting proteolipid protein (PLP)-induced, along the disease progression, using advanced magnetic resonance imaging (MRI) parameters. The emphasis of this study was the overall assessment of the whole brain by histogram analysis, as well as the detection of specific affected regions by voxel based analysis (VBA) using quantitative T2, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Brains of EAE-inflicted mice from both models revealed multiple white and gray matter areas with significant changes from naïve mice for all MRI parameters. Ventricle swelling was more characteristic to the PLP-induced model. Decreased MTR values and increased apparent diffusion coefficient (ADC) were observed mainly in MOG-induced EAE, indicative of macromolecular loss and structural CNS damage involvement in the chronic disease. The MS drug glatiramer acetate (GA), applied either as prevention or therapeutic treatment, affected all the MRI pathological manifestations, resulting in reduced T2 values and ventricle volume, elevated MTR and decreased ADC, in comparison to untreated EAE-inflicted mice. In accord, immunohistochemical analysis indicated less histological damage and higher amount of proliferating oligodendrocyte progenitor cells after GA treatment. The higher brain tissue integrity reflected by the MRI parameters on the level of the whole brain and in specific regions supports the in situ anti-inflammatory and neuroprotective consequences of GA treatment.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Elsevier
ISSN: 0014-4886
Last Modified: 21 Aug 2019 02:19
URI: https://orca.cardiff.ac.uk/id/eprint/91873

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