Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Schampel, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Volovitch, Oleg UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeniger, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Scholz, Claus-Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Joerge, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Linker, Ralf A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wischmeyer, Erhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunsch, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hell, Johannes W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erguen, Sueleyman UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuerten, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GATED POTASSIUM CHANNELS; SODIUM-CHANNELS; AXONAL INJURY; WHITE-MATTER; NITRIC-OXIDE; ACTIVATION; HIPPOCAMPAL; NEUROPROTECTION; PATHOLOGY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23383