Amatruda, Mario;
Harris, Kate;
Matis, Alina;
Davies, Andrew L;
McElroy, Daniel;
Clark, Michael;
Linington, Christopher;
... Smith, Kenneth J; + view all
(2023)
Oxygen treatment reduces neurological deficits and demyelination in two animal models of multiple sclerosis.
Neuropathol Appl Neurobiol
, 49
(1)
, Article e12868. 10.1111/nan.12868.
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Neuropathology Appl Neurobio - 2022 - Amatruda - Oxygen treatment reduces neurological deficits and demyelination in two.pdf - Published Version Download (4MB) | Preview |
Abstract
AIMS: To explore the importance of tissue hypoxia in causing neurological deficits and demyelination in the inflamed CNS, and the value of inspiratory oxygen treatment, using both active and passive experimental autoimmune encephalomyelitis (EAE). METHODS: Normobaric oxygen treatment was administered to Dark Agouti rats with either active or passive EAE, compared with room air-treated, and naïve, controls. RESULTS: Severe neurological deficits in active EAE were significantly improved after just 1 hour of breathing ~95% oxygen. The improvement was greater and more persistent when oxygen was applied either prophylactically (from immunization for 23 days), or therapeutically from the onset of neurological deficits for 24, 48, or 72 hours. Therapeutic oxygen for 72 hours significantly reduced demyelination and the integrated stress response in oligodendrocytes at the peak of disease, and protected from oligodendrocyte loss, without evidence of increased oxidative damage. T-cell infiltration and cytokine expression in the spinal cord remained similar to that in untreated animals. The severe neurological deficit of animals with passive EAE occurred in conjunction with spinal hypoxia and was significantly reduced by oxygen treatment initiated before their onset. CONCLUSIONS: Severe neurological deficits in both active and passive EAE can be caused by hypoxia and reduced by oxygen treatment. Oxygen treatment also reduces demyelination in active EAE, despite the autoimmune origin of the disease.
| Type: | Article |
|---|---|
| Title: | Oxygen treatment reduces neurological deficits and demyelination in two animal models of multiple sclerosis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/nan.12868 |
| Publisher version: | https://doi.org/10.1111/nan.12868 |
| Language: | English |
| Additional information: | © 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | EAE, Neuroinflammation, hypoxia, integrated stress response, oxidative damage, oxygen treatment |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10163332 |
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