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Mouse model mimics multiple sclerosis in the clinico-radiological paradox

Item Type:Article
Title:Mouse model mimics multiple sclerosis in the clinico-radiological paradox
Creators Name:Wuerfel, J. and Tysiak, E. and Prozorovski, T. and Smyth, M. and Mueller, S. and Schnorr, J. and Taupitz, M. and Zipp, F.
Abstract:The value of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, in deriving novel diagnostic and therapeutic input has been subject to recent debate. This study is the first to report a disseminated distribution of plaques including cranial nerves, prior to or at early stages of disease in murine adoptive transfer EAE, irrespective of the development of clinical symptoms. We induced EAE by adoptive proteolipid protein-specific T-cell transfer in 26 female SJL/J mice, and applied high-field-strength magnetic resonance imaging (MRI) scans longitudinally, assessing blood–brain barrier (BBB) disruption by gadopentate dimeglumine enhancement. We visualized inflammatory nerve injury by gadofluorine M accumulation, and phagocytic cells in inflamed tissue by very small anionic iron oxide particles (VSOP-C184). MRI was correlated with immunohistological sections. In this study, we discovered very early BBB breakdown of white and grey brain matter in 25 mice; one mouse developed exclusively spinal cord inflammation. Widely disseminated contrast-enhancing lesions preceded the onset of disease in 10 animals. Such lesions were present despite the absence of any clinical disease formation in four mice, and coincided with the first detectable symptoms in others. Cranial nerves, predominantly the optic and trigeminal nerves, showed signal intensity changes in nuclei and fascicles of 14 mice. At all sites of MRI lesions we detected cellular infiltrates on corresponding histological sections. The discrepancy between the disease burden visualized by MRI and the extent of disability indeed mimics the human clinico-radiological paradox. MRI should therefore be implemented into evaluational in vivo routines of future therapeutic EAE studies.
Keywords:Blood-brain barrier, Cranial nerve, EAE, Multiple sclerosis, Animals, Mice
Source:European Journal of Neuroscience
Publisher:Blackwell Publishing
Page Range:190-198
Date:July 2007
Additional Information:The definitive version is available at www.blackwell-synergy.com
Official Publication:https://doi.org/10.1111/j.1460-9568.2007.05644.x
PubMed:View item in PubMed

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