title: Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis.
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.
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, 97070 Wuerzburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schampel
authors.affiliation: Department of Anatomy and Cell Biology, University of Cologne, 50931 Cologne, Germany.
authors.forename: Oleg
authors.initials: O
authors.lastname: Volovitch
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, 97070 Wuerzburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Koeniger
authors.affiliation: Core Unit Systems Medicine, University Hospital of Würzburg, 97080 Wuerzburg, Germany.|The Life & Medical Sciences Institute, University of Bonn, 53113 Bonn, Germany.
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jörg
authors.affiliation: Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.affiliation: Institute of Physiology, Molecular Electrophysiology, University of Würzburg, 97070 Wuerzburg, Germany.
authors.forename: Erhard
authors.initials: E
authors.lastname: Wischmeyer
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, 97070 Wuerzburg, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Wunsch
authors.affiliation: Department of Pharmacology, University of California, Davis, CA 95616.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, 97070 Wuerzburg, Germany.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, 97070 Wuerzburg, Germany; stefanie.kuerten@fau.de.
authors.forename: Stefanie
authors.identifier: 0000-0001-6119-605X
authors.initials: S
authors.lastname: Kuerten
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009553:Nimodipine / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000074586:Remyelination / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D020746:Calcium Channels, L-Type; D017382:Reactive Oxygen Species; D009553:Nimodipine; D052247:Nitric Oxide Synthase Type II
keywords: EAE; MS; microglia; neuroprotection; nimodipine