title: Hyperoxic resuscitation after hypoxia-ischemia induces cerebral inflammation that is attenuated by tempol in a reporter mouse model with very young mice.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatric Research, University of Oslo and Oslo University Hospital, Oslo, Norway. gaute.dohlen@ous-hf.no
authors.forename: Gaute
authors.initials: G
authors.lastname: Døhlen
authors.forename: Ellen-Ann
authors.initials: EA
authors.lastname: Antal
authors.forename: Albert
authors.initials: A
authors.lastname: Castellheim
authors.forename: Erik
authors.initials: E
authors.lastname: Thaulow
authors.forename: Anders
authors.initials: A
authors.lastname: Kielland
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use; D001238:Asphyxia Neonatorum / Q000150:complications / Q000628:therapy*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D017930:Genes, Reporter; D006801:Humans; D018496:Hyperoxia / Q000150:complications*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000628:therapy*; D007231:Infant, Newborn; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D012151:Resuscitation / Q000009:adverse effects*; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D016207:Cytokines; D016166:Free Radical Scavengers; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013113:Spin Labels; D008156:Luciferases; C001803:tempol