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Brain Advance Access published online on May 19, 2006
Brain, doi:10.1093/brain/awl135
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received February 8, 2006
Revised April 21, 2006
Accepted April 24, 2006

Article

A new focal EAE model of cortical demyelination: multiple sclerosis-like lesions with rapid resolution of inflammation and extensive remyelination

Doron Merkler 1, Tristan Ernsting 1, Martin Kerschensteiner 2, Wolfgang Brück 3 * *, and Christine Stadelmann 1 *

1 Department of Neuropathology, Georg-August University, Göttingen, Germany
2 Research Unit ‘Therapy Development’, Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, Munich, Germany
3 Department of Neuropathology, Georg-August University, Göttingen, Germany; Institut für Multiple-Sklerose-Forschung, Bereich Humanmedizin der Georg-August Universität Göttingen und Gemeinnützige Hertie-Stiftung, Göttingen, Germany

* To whom correspondence should be addressed.
Wolfgang Brück, E-mail: wbrueck{at}med.uni-goettingen.de


  Abstract

Recent studies have revealed widespread demyelination in the cortex of patients with chronic multiple sclerosis. In contrast to white matter lesions, cortical multiple sclerosis lesions are accompanied by only minor inflammation. Research into the pathogenesis of cortical lesion formation has been hampered by the fact that the conventional rodent model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), does not regularly affect the cortex. To overcome this limitation we developed a new rat model of cortical multiple sclerosis. Lesions were stereotactically targeted to the cerebral cortex by injection of pro-inflammatory mediators in animals that were immunized subclinically with myelin oligodendrocyte glycoprotein (MOG). We thus generated highly reproducible demyelinated lesions in the neocortex with remarkable histological similarities to cortical multiple sclerosis lesions. The focal cortical EAE model led to the typical pattern of intracortical and subpial demyelination, infiltration with inflammatory cells, complement deposition, acute axonal damage and neuronal cell death. Surprisingly, extensive cortical inflammation largely resolved within 2 weeks. Furthermore, cortical demyelination was readily compensated by rapid remyelination. Our data thus suggest that cortical inflammation is a transient phenomenon, and that remyelination of cortical inflammatory-demyelinating lesions may occur rapidly.

Keywords: neuroinflammation; multiple sclerosis; neuroimmunology; cortex; EAE.
*These authors have contributed equally to this work as co-senior authors.
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