Chisholm, Kim I;
Ida, Keila K;
Davies, Andrew L;
Tachtsidis, Ilias;
Papkovsky, Dmitri B;
Dyson, Alex;
Singer, Mervyn;
Duchen, Michael R;
Smith, Kenneth J
Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis
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Media type:
E-Article
Title:
Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis
Contributor:
Chisholm, Kim I;
Ida, Keila K;
Davies, Andrew L;
Tachtsidis, Ilias;
Papkovsky, Dmitri B;
Dyson, Alex;
Singer, Mervyn;
Duchen, Michael R;
Smith, Kenneth J
Published:
SAGE Publications, 2016
Published in:
Journal of Cerebral Blood Flow & Metabolism, 36 (2016) 11, Seite 1955-1964
Language:
English
DOI:
10.1177/0271678x15606457
ISSN:
0271-678X;
1559-7016
Origination:
Footnote:
Description:
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.