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Continuous cuprizone intoxication allows active experimental autoimmune encephalomyelitis induction in C57BL/6 mice

  • Vladislav Yakimov
  • Felix Schweiger
  • Jiangshan Zhan
  • Newshan Behrangi
  • Anja Horn
  • Christoph Schmitz
  • Tanja Hochstrasser
  • Markus KippEmail author
Original Paper

Abstract

Oligodendrocyte degeneration is a hallmark of multiple sclerosis pathology, and protecting oligodendrocytes and myelin is likely to be of clinical relevance. Traditionally, oligodendrocyte and myelin degeneration are viewed as a direct consequence of an inflammatory attack, but metabolic defects might be equally important. Appropriate animal models to study the interplay of inflammation and metabolic injury are, therefore, needed. Here, we describe that in spite of its immunosuppressive effects, a continuous intoxication with cuprizone allows the induction of active experimental autoimmune encephalomyelitis (EAE) by myelin oligodendrocyte glycoprotein (MOG35–55) immunization. Although the clinical severity of EAE is ameliorated in cuprizone-intoxicated mice, the recruitment of granulocytes, and especially, CD3+ lymphocytes into the forebrain is triggered by the cuprizone insult. Such combined lesions are further characterized by oligodendrocyte apoptosis and microglia activation, closely mimicking type III multiple sclerosis lesions. In summary, we provide a protocol that allows to study the direct interplay of immune-mediated and metabolic oligodendrocyte injury and its consequences for the cerebral white and grey matters.

Keywords

Multiple sclerosis Oligodendrocyte injury Neuroinflammation Peripheral immune-cell recruitment 

Notes

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (KI 1469/8-1; MK). We thank Astrid Baltruschat, Beate Aschauer, Barbara Mosler, Sabine Tost, Sibylle Kerling and Sarah Wübbel for their excellent and valuable technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

418_2019_1786_MOESM1_ESM.tif (5.4 mb)
Supplementary material 1 (TIFF 5574 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of Anatomy II, Faculty of MedicineLMU MunichMunichGermany
  2. 2.Institute of AnatomyRostock University Medical CenterRostockGermany
  3. 3.Institute of Anatomy I, Faculty of MedicineLMU MunichMunichGermany

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