Journal Article

Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage

Stefan Nessler, Susann Boretius, Christine Stadelmann, Alwina Bittner, Doron Merkler, Hans-Peter Hartung, Thomas Michaelis, Wolfgang Brück, Jens Frahm, Norbert Sommer and Bernhard Hemmer

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 8, pages 2186-2198
Published in print August 2007 | ISSN: 0006-8950
Published online July 2007 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awm105
Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage

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MRI is routinely used for in vivo detection of multiple sclerosis (MS) lesions. Histopathological correlates of MRI signal alterations are still poorly defined. In the present study, we describe a mouse model of MS presenting with inflammatory brain lesions. During the acute disease phase, two independent lesion patterns were identified by T1- and T2-weighted high-resolution 3D MRI: lesions with reduced signal intensity on both T1- and T2-weighted images (type A) and lesions with slightly reduced signal intensity on T1-weighted images and increased signal intensity on T2-weighted images (type B). Type A lesions were characterized by significantly denser inflammatory cell infiltrates and more myelin loss than type B lesions. Lesion cellularity, myelin loss and immunoglobulin deposition correlated with MRI signal intensities in both lesion types. Gd-DTPA enhancement correlated with Ig deposition and spacially matched to areas with abundant activated microglia cells at the lesion border. Using serial MRI, type A lesions revealed a persistent hypointense pattern reflecting axon and myelin loss. Signal intensity increases on T2-weighted images of type B lesions decreased during lesion evolution, and no significant T1 signal alterations developed. Taken together, MRI of mouse EAE models with brain lesions provide new insights into lesion pathology and evolution and may prove useful for the in vivo assessment of new therapeutic strategies in MS.

Keywords: magnetic resonance imaging (MRI); experimental autoimmune encephalomyelitis (EAE); histopathology; T-cell clone; multiple sclerosis

Journal Article.  7217 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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