Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis

Journal of Neurochemistry
Jens IngwersenTim Prozorovski

Abstract

Multiple sclerosis (MS) is characterized by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca2+overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca2+influx by pharmacological modulation of Ca2+channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy. We therefore investigated the effects of the L-type voltage-gated calcium channel (VGCC) blocker nimodipine in two different models of mouse experimental autoimmune encephalomyelitis (EAE), an established experimental paradigm for MS. We show that preventive application of nimodipine (10 mg/kg per day) starting on the day of induction had ameliorating effects on EAE in SJL/J mice immunized with encephalitic myelin peptide PLP139-151, specifically in late-stage disease. Furthermore, supporting these data, administration of nimodipine to MOG35-55-immunized C57BL/6 mice starting at the peak of pre-established disease, also led to a significant decrease ...Continue Reading

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Citations

Mar 4, 2020·International Journal of Molecular Sciences·Michael EndersStefanie Kuerten
Apr 18, 2020·Expert Opinion on Investigational Drugs·Pablo Villoslada, Lawrence Steinman
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Jul 25, 2021·International Journal of Molecular Sciences·Federica CherchiElisabetta Coppi
Nov 21, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yunwei HuDan Liang

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