Tim Clarner and Felix Diederichs contributed equally as first authors. Sandra Amor and Markus Kipp contributed equally as last authors.
Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions†
Article first published online: 11 JUN 2012
Copyright © 2012 Wiley Periodicals, Inc.
Volume 60, Issue 10, pages 1468–1480, October 2012
How to Cite
Clarner, T., Diederichs, F., Berger, K., Denecke, B., Gan, L., van der Valk, P., Beyer, C., Amor, S. and Kipp, M. (2012), Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions. Glia, 60: 1468–1480. doi: 10.1002/glia.22367
- Issue published online: 16 AUG 2012
- Article first published online: 11 JUN 2012
- Manuscript Accepted: 14 MAY 2012
- Manuscript Revised: 9 MAY 2012
- Manuscript Received: 31 JUL 2011
- START grants of the Medical Faculty, RWTH Aachen
- The Deutsche Forschungsgemeinschaft
- B. Braun Melsungen Stiftung, Stichting MS Research and the MS Society of Great Britain and Northern Ireland
- gray matter;
In multiple sclerosis (MS), gray matter pathology is characterized by less pronounced inflammation when compared with white matter lesions. Although regional differences in the cytoarchitecture may account for these differences, the amount of myelin debris in the cortex during a demyelinating event might also be contributory. To analyze the association between myelin debris levels and inflammatory responses, cortical areas with distinct and sparse myelination were analyzed for micro- and astrogliosis before and after cuprizone-induced demyelination in mice. In postmortem tissue of MS patients, leucocortical lesions were assessed for the type and level of inflammation in the cortical and white matter regions of the lesion. Furthermore, mice were injected intracerebrally with myelin-enriched debris, and the inflammatory response analyzed in white and grey matter areas. Our studies show that the magnitude of myelin loss positively correlates with microgliosis in the cuprizone model. In MS, the number of MHC class II expressing cells is higher in the white compared with the grey matter part of leucocortical lesions. Finally, direct application of myelin debris into the corpus callosum or cortex of mice induces profound and comparable inflammation in both regions. Our data suggest that myelin debris is an important variable in the inflammatory response during demyelinating events. Whether myelin-driven inflammation affects neuronal integrity remains to be clarified. © 2012 Wiley Periodicals, Inc.