Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis

Autor: Marie Wunsch, Johannes W. Hell, Erhard Wischmeyer, Oleg Volovitch, Stefanie Kuerten, Andrea Schampel, Tobias Koeniger, Claus Jürgen Scholz, Ralf A. Linker, Süleyman Ergün, Stefanie Jörg
Rok vydání: 2017
Předmět:
0301 basic medicine
Nitric Oxide Synthase Type II
microglia
Apoptosis
Pharmacology
Neurodegenerative
Mice
0302 clinical medicine
Encephalomyelitis
Cells
Cultured
Multidisciplinary
Cultured
Microglia
EAE
Neurodegeneration
Experimental autoimmune encephalomyelitis
L-Type
Oligodendroglia
medicine.anatomical_structure
PNAS Plus
Spinal Cord
Neurological
neuroprotection
medicine.drug
Encephalomyelitis
Autoimmune
Experimental
Multiple Sclerosis
Calcium Channels
L-Type
Cells
1.1 Normal biological development and functioning
Neuroprotection
Autoimmune Disease
03 medical and health sciences
Experimental
Underpinning research
medicine
Animals
Remyelination
Nimodipine
business.industry
Animal
Multiple sclerosis
Neurosciences
MS
nimodipine
medicine.disease
Neuroregeneration
Brain Disorders
Disease Models
Animal
030104 developmental biology
Immunology
Disease Models
Calcium Channels
business
Reactive Oxygen Species
030217 neurology & neurosurgery
Autoimmune
Zdroj: Proceedings of the National Academy of Sciences of the United States of America, vol 114, iss 16
Popis: 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.
Databáze: OpenAIRE
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