Brain Advance Access originally published online on July 7, 2007
Brain 2007 130(8):2186-2198; doi:10.1093/brain/awm105
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Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage
1Department of Neurology, Heinrich-Heine-University Düsseldorf; 2Clinical Neuroimmunology Group, Department of Neurology, Klinikum rechts der Isar, Technical University Munich; 3Biomedizinische NMR Forschungs GmbH and Max-Planck-Institut for biophysikalische Chemie Göttingen; 4Institute of Neuropathology, Georg-August-University Göttingen and 5Clinical Neuroimmunology Group, Department of Neurology, Philipps-University Marburg
Correspondence to: Dr Bernhard Hemmer, Department of Neurology, Klinikum rechts der Isar, Technische Universität, Ismaninger Str. 21, Munich, Germany E-mail: hemmer{at}lrz.tu-muenchen.de
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.
Key Words: magnetic resonance imaging (MRI); experimental autoimmune encephalomyelitis (EAE); histopathology; T-cell clone; multiple sclerosis
Abbreviations: APC, antigen presenting cell; BBB, blood–brain barrier; CNP, cyclic nucleotide phosphodiesterase; EAE, experimental autoimmune encephalomyelitis; GFAP, glial fibrillary acidic protein; Ig, immunoglobulin; MBP, myelin basic protein; MS, multiple sclerosis; PLP, proteolipid protein; PMN, polymorphonuclear cell
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Received November 21, 2006. Revised March 29, 2007. Accepted April 12, 2007.
*These authors are the joint First Authors.
These authors are the joint Last Authors.
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  B. Brochet, V. Dousset, M. Deloire, C. Boiziau, and K. G. Petry MRI to predict severe tissue damage in inflammatory lesions in animal models of multiple sclerosis Brain, March 1, 2008; 131(3): e92 - e92. [Full Text] [PDF]
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