Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis

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dc.contributor.author Chisholm, Kim I.
dc.contributor.author Ida, Keila K.
dc.contributor.author Davies, Andrew L.
dc.contributor.author Tachtsidis, Ilias
dc.contributor.author Papkovsky, Dmitri B.
dc.contributor.author Dyson, Alex
dc.contributor.author Singer, Mervyn
dc.contributor.author Duchen, Michael R.
dc.contributor.author Smith, Kenneth J.
dc.date.accessioned 2016-11-30T10:01:53Z
dc.date.available 2016-11-30T10:01:53Z
dc.date.issued 2015-11-25
dc.identifier.citation Chisholm, K. I., Ida, K. K., Davies, A. L., Tachtsidis, I., Papkovsky, D. B., Dyson, A., Singer, M., Duchen, M. R., Smith, K. J. (2016) 'Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis'. Journal Of Cerebral Blood Flow And Metabolism, 36 (1111):1955-1964. doi: 10.1177/0271678X15606457 en
dc.identifier.volume 36 en
dc.identifier.issued 1111 en
dc.identifier.startpage 1955 en
dc.identifier.endpage 1964 en
dc.identifier.issn 0271-678X
dc.identifier.uri http://hdl.handle.net/10468/3327
dc.identifier.doi 10.1177/0271678X15606457
dc.description.abstract Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.01 ml/g; n = 47). Six, 24 and 48 h later, we used confocal imaging in vivo to assess cerebral mitochondrial redox potential and cortical oxygenation in response to changes in inspired oxygen. The fraction of inspired oxygen (FiO2) at which the cortical redox potential changed was compared between groups. In a subset of animals, spontaneous hypothermia was maintained or controlled hypothermia induced during imaging. Decreasing FiO2 resulted in a more reduced cerebral redox state around veins, but preserved oxidation around arteries. This pattern appeared at a higher FiO2 in LPS-injected animals, suggesting an increased sensitivity of cortical mitochondria to hypoxemia. This increased sensitivity was accompanied by a decrease in cortical oxygenation, but was attenuated by hypothermia. These results suggest that systemic endotoxemia influences cortical oxygenation and mitochondrial function, and that therapeutic hypothermia can be protective. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Sage Publications en
dc.rights © Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). en
dc.rights.uri http://www.creativecommons.org/licenses/by/3.0/ en
dc.subject Imaging en
dc.subject Hypothermia en
dc.subject Microcirculation en
dc.subject Inflammation en
dc.subject Microscopy en
dc.title Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Dmitri Papkovsky, School Of Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: d.papkovsky@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2016-11-30T09:51:34Z
dc.description.version Published Version en
dc.internal.rssid 373873185
dc.contributor.funder University College London en
dc.contributor.funder Multiple Sclerosis Society en
dc.contributor.funder National Multiple Sclerosis Society en
dc.contributor.funder Wellcome Trust en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal Of Cerebral Blood Flow And Metabolism en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress d.papkovsky@ucc.ie en


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© Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). Except where otherwise noted, this item's license is described as © Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
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