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Journal of Neuroinflammation

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Open Access 01-12-2016 | Research

Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE

Authors: Nilufer Esen, Vladimir Katyshev, Zakhar Serkin, Svetlana Katysheva, Paula Dore-Duffy

Published in: Journal of Neuroinflammation | Issue 1/2016

Abstract

Background

In the brain, chronic inflammatory activity may lead to compromised delivery of oxygen and glucose suggesting that therapeutic approaches aimed at restoring metabolic balance may be useful. In vivo exposure to chronic mild normobaric hypoxia (10 % oxygen) leads to a number of endogenous adaptations that includes vascular remodeling (angioplasticity). Angioplasticity promotes tissue survival. We have previously shown that induction of adaptive angioplasticity modulates the disease pattern in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). In the present study, we define mechanisms by which adaptation to low oxygen functionally ameliorates the signs and symptoms of EAE and for the first time show that tissue hypoxia may fundamentally alter neurodegenerative disease.

Methods

C57BL/6 mice were immunized with MOG, and some of them were kept in the hypoxia chambers (day 0) and exposed to 10 % oxygen for 3 weeks, while the others were kept at normoxic environment. Sham-immunized controls were included in both hypoxic and normoxic groups. Animals were sacrificed at pre-clinical and peak disease periods for tissue collection and analysis.

Results

Exposure to mild hypoxia decreased histological evidence of inflammation. Decreased numbers of cluster of differentiation (CD)4+ T cells were found in the hypoxic spinal cords associated with a delayed Th17-specific cytokine response. Hypoxia-induced changes did not alter the sensitization of peripheral T cells to the MOG peptide. Exposure to mild hypoxia induced significant increases in anti-inflammatory IL-10 levels and an increase in the number of spinal cord CD25+FoxP3+ T-regulatory cells.

Conclusions

Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.

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Title: Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE
Authors: Nilufer Esen
Vladimir Katyshev
Zakhar Serkin
Svetlana Katysheva
Paula Dore-Duffy
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-015-0407-4

At a glance: The STEP trials

Springer Medicine

Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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