title: Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE.
abstract: Most multiple sclerosis (MS) patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in MS is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS) macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic MS. Here, we employ intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1-4, DUOX1, 2) and, thus, to identify the cellular source of oxidative stress in the CNS of mice affected by experimental autoimmune encephalomyelitis (EAE) in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET-FLIM, providing a possible mechanism of disease progression in MS.
authors.affiliation: Department of Neuropathology, Charité - Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Radbruch
authors.affiliation: German Rheumatism Research Center (DRFZ) a Leibniz Institute , Berlin , Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bremer
authors.affiliation: German Rheumatism Research Center (DRFZ) a Leibniz Institute , Berlin , Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Guenther
authors.affiliation: German Rheumatism Research Center (DRFZ) a Leibniz Institute , Berlin , Germany.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Cseresnyes
authors.affiliation: German Rheumatism Research Center (DRFZ) a Leibniz Institute , Berlin , Germany.
authors.forename: Randall
authors.initials: R
authors.lastname: Lindquist
authors.affiliation: German Rheumatism Research Center (DRFZ) a Leibniz Institute, Berlin, Germany; Immundynamics, Charité - Universiätsmedizin Berlin, Berlin, Germany.
authors.forename: Anja E
authors.initials: AE
authors.lastname: Hauser
authors.affiliation: German Rheumatism Research Center (DRFZ) a Leibniz Institute , Berlin , Germany.
authors.forename: Raluca
authors.initials: R
authors.lastname: Niesner
keywords: EAE/MS; FLIM–FRET; NOX; calcium; intravital imaging