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Hyperoxic resuscitation after hypoxia-ischemia induces cerebral inflammation that is attenuated by tempol in a reporter mouse model with very young mice

  • Gaute Døhlen EMAIL logo , Ellen-Ann Antal , Albert Castellheim , Erik Thaulow , Anders Kielland and Ola Didrik Saugstad
Published/Copyright: November 15, 2012

Abstract

Background: Oxygen supplementation is still part of international resuscitation protocols for premature children. Mechanisms for tissue damage by hypoxia/ischemia in the extreme premature involve inflammation.

Aim and method: To study cerebral inflammation after hypoxia/ischemia and oxygen treatment in the premature, we measured NF-κB activity in 5-day-old transgenic reporter mice in response to experimental hypoxia/ischemia. Results were correlated to cerebral histological evaluation and plasma cytokine levels. A treatment strategy with the antioxidant tempol was tested.

Results: One day after hypoxia/ischemia NF-κB activation was increased compared to controls [mean difference: 10.6±4.6% (P=0.03)]. Exposure to 100% oxygen after hypoxia/ischemia further increased NF-κB activation compared to hypoxia/ischemia alone [mean difference: 15.0±5.5% (P=0.01)]. Histological changes in the brain were positively correlated with NF-κB activity (P<0.001), but we found no significant difference in tissue damage between resuscitation with air and resuscitation with pure oxygen. Administration of tempol reduced NF-κB activation [mean difference: 14.6±5.0% (P=0.01)] and the plasma level of cytokines; however, the histological damage score was not affected.

Conclusion: Cerebral inflammatory response after hypoxia/ischemia in a mouse model with immature brain development corresponding to human prematurity prior to 32 weeks’ gestation was influenced by administration of oxygen. Tempol treatment attenuated inflammation but did not reduce the extent of histological cerebral damage.


Corresponding author: Gaute Døhlen, Department of Paediatric Research, University of Oslo and Oslo University Hospital, Oslo, Norway

The authors stated that there are no conflicts of interest regarding the publication of this article.

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Received: 2012-6-8
Accepted: 2012-10-16
Published Online: 2012-11-15
Published in Print: 2013-05-01

©2013 by Walter de Gruyter Berlin Boston

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