title: Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat.
abstract: BACKGROUND
  Mild therapeutic hypothermia (HT) reduces brain injury in survivors after perinatal asphyxia. Recent guidelines suggest that resuscitation of term infants should be started with air, but supplemental oxygen is still in use. It is not known whether supplemental oxygen during resuscitation affects the protection offered by subsequent HT.
  
  
  RESULTS
  Wilcoxon median (95% confidence interval) hippocampal injury scores (range 0.0-4.0; 0 to ≥90% injury) were 21% O(2) normothermia (NT): 2.00 (1.25-2.50), 21% O(2) HT: 1.00 (0.50-1.50), 100% O(2) NT: 2.50 (1.50-3.25), and 100% O(2) HT: 2.00 (1.25-2.50). Although HT significantly reduced hippocampal injury (B = -0.721, SEM = 0.297, P = 0.018), reoxygenation with 100% O(2) increased injury (B = +0.647, SEM = 0.297, P = 0.033). Regression constant B = 1.896, SEM = 0.257 and normally distributed residuals.
  
  
  CONCLUSIONS
  We confirm an ~50% neuroprotective effect of therapeutic HT in the neonatal rat. Reoxygenation with 100% O(2) increased injury and worsened reflex performance. HT was neuroprotective whether applied after reoxygenation with air or 100% O(2). However, HT after 100% O(2) gave no net neuroprotection.
  
  
  METHODS
  In an established neonatal rat model, hypoxia-ischemia (HI) was followed by 30-min reoxygenation in either 21% O(2) or 100% O(2) before 5 h of NT (37 °C) or HT (32 °C). The effects of HT and 100% O(2) on histopathologic injury in the hippocampus, basal ganglia, and cortex, and on postural reflex performance 7 d after the insult, were estimated by linear regression.
authors.affiliation: Department of Pediatric Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Marit L
authors.initials: ML
authors.lastname: Dalen
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: Maja
authors.initials: M
authors.lastname: Elstad
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Ola D
authors.initials: OD
authors.lastname: Saugstad
authors.forename: Terje
authors.initials: T
authors.lastname: Rootwelt
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001237:Asphyxia / Q000150:complications / Q000628:therapy*; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000139:chemically induced* / Q000209:etiology / Q000517:prevention & control*; D016014:Linear Models; D008297:Male; D023421:Models, Animal; D010100:Oxygen / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D010100:Oxygen