Teriflunomide's Effect on Glia in Experimental Demyelinating Disease: A Neuroimaging and Histologic Study

Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging
Suyog PolRobert Zivadinov

Abstract

Teriflunomide reduces disability progression and brain atrophy in multiple sclerosis patients. The exact mechanism of action by which teriflunomide exerts these effects is currently unknown. We assessed the effect of teriflunomide on brain glial cells in the Theiler's murine encephalomyelitis virus (TMEV) by using a histological approach in combination with neuroimaging. Forty-eight SJL female mice received an intracerebral injection of TMEV at 6-8 weeks of age and were then treated with teriflunomide (n = 24) or placebo (n = 24) for 9 months. They were examined with MRI and behavioral testing at 2, 6, and 9 months postinduction (mPI). Of those, 18 teriflunomide-treated and 17 controls mice were analyzed histologically at 9 mPI to sample from different brain regions for myelination status, microglial density, and oligodendroglial lineage. The histological and MRI outcomes were correlated. Corpus callosum microglial density was numerically lower in the teriflunomide-treated mice compared to the control group (141.1 ± 21.7 SEM vs. 214.74 ± 34.79 SEM, Iba1+ cells/mm2 , P = .087). Basal ganglia (BG) microglial density in the teriflunomide group exhibited a negative correlation with fractional anisotropy (P = .021) and a positive co...Continue Reading

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Citations

Mar 14, 2019·Current Opinion in Neurology·David KremerPatrick Küry
Sep 1, 2020·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Robert ZivadinovSuyog Pol
Jun 21, 2020·International Journal of Molecular Sciences·Madeline BrossEvanthia Bernitsas
Jun 18, 2020·International Journal of Molecular Sciences·Kim M A De Kleijn, Gerard J M Martens
Oct 22, 2020·ELife·Matteo ManciniNikola Stikov
Oct 14, 2021·Neurology. Neuroimmunology and Neuroinflammation·Elodie MartinBruno Stankoff

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