Schampel, Andrea, Volovitch, Oleg, Koeniger, Tobias, Scholz, Claus-Juergen, Joerge, Stefanie, Linker, Ralf A., Wischmeyer, Erhard, Wunsch, Marie, Hell, Johannes W., Erguen, Sueleyman and Kuerten, Stefanie (2017). Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis. Proc. Natl. Acad. Sci. U. S. A., 114 (16). S. E3295 - 10. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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Abstract

Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated clinical EAE and spinal cord degeneration and promoted remyelination. Surprisingly, we observed calcium channel-independent effects on microglia, resulting in apoptosis. These effects were cell-type specific and irrespective of microglia polarization. Apoptosis was accompanied by decreased levels of nitric oxide (NO) and inducible NO synthase (iNOS) in cell culture as well as decreased iNOS and reactive oxygen species levels in EAE. In addition, increased numbers of Olig2(+) APC(+) oligodendrocytes were detected. Overall, nimodipine application seems to generate a favorable environment for regenerative processes and therefore could be a treatment option for MS, because it combines features of immunomodulation with beneficial effects on neuroregeneration.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schampel, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volovitch, OlegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeniger, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholz, Claus-JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joerge, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Linker, Ralf A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wischmeyer, ErhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunsch, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hell, Johannes W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erguen, SueleymanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuerten, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-233836
DOI: 10.1073/pnas.1620052114
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 114
Number: 16
Page Range: S. E3295 - 10
Date: 2017
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GATED POTASSIUM CHANNELS; SODIUM-CHANNELS; AXONAL INJURY; WHITE-MATTER; NITRIC-OXIDE; ACTIVATION; HIPPOCAMPAL; NEUROPROTECTION; PATHOLOGYMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23383

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