Oxidative injury and iron redistribution are pathological hallmarks of marmoset experimental autoimmune encephalomyelitis

Jordon Dunham, Jan Bauer, Graham R. Campbell, Don J. Mahad, Nikki van Driel, Susanne M.A. van der Pol, Bert A. 't Hart, Hans Lassmann, Jon D. Laman, Jack van Horssen, Yolanda S. Kap*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE lesion-associated liberation of iron (due to loss of ironcontaining myelin) was associated with altered expression of the iron metabolic markers FtH1, lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative damage markers in inflammatory lesions indicates that the enhanced antioxidant enzyme expression could not counteract reactive oxygen and nitrogen species-induced cellular damage, as is also observed in MS brains. This study demonstrates that oxidative injury and aberrant iron distribution are prominent pathological hallmarks of marmoset EAE thus making this model suitable for therapeutic intervention studies aimed at reducing oxidative stress and associated iron dysmetabolism.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume76
Issue number6
DOIs
Publication statusPublished - 2017

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