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Publication Detail
Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Chisholm KI, Ida KK, Davies AL, Tachtsidis I, Papkovsky DB, Dyson A, Singer M, Duchen MR, Smith KJ
  • Publisher:
    Nature Publishing Group
  • Publication date:
    01/11/2016
  • Journal:
    Journal of Cerebral Blood Flow and Metabolism
  • Status:
    Accepted
  • Print ISSN:
    1559-7016
  • Addresses:
    Institute of Neurology
    Department of Neuroinflammation
    London
    WC1N 1PJ
    United Kingdom
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 48h 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.
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Cell & Developmental Biology
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Nephrology
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Neuroinflammation
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Dept of Med Phys & Biomedical Eng
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