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Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation

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Item Type:Article
Title:Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation
Creators Name:Mossakowski, A.A. and Pohlan, J. and Bremer, D. and Lindquist, R. and Millward, J.M. and Bock, M. and Pollok, K. and Mothes, R. and Viohl, L. and Radbruch, M. and Gerhard, J. and Bellmann-Strobl, J. and Behrens, J. and Infante-Duarte, C. and Mähler, A. and Boschmann, M. and Rinnenthal, J.L. and Füchtemeier, M. and Herz, J. and Pache, F.C. and Bardua, M. and Priller, J. and Hauser, A.E. and Paul, F. and Niesner, R. and Radbruch, H.
Abstract:The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation.
Keywords:Multiple Sclerosis, Oxidative Stress, Neuronal Dysfunction, Fluorescence Lifetime Microscopy, Intravital Imaging, Oxidative Stress Memory, Animals, Mice
Source:Acta Neuropathologica
Page Range:799-814
Date:December 2015
Official Publication:https://doi.org/10.1007/s00401-015-1497-x
PubMed:View item in PubMed

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