title: Rectal temperature in the first five hours after hypoxia-ischemia critically affects neuropathological outcomes in neonatal rats.
abstract: BackgroundHyperthermia after hypoxia-ischemia (HI) in newborn infants is associated with worse neurological outcomes. Loss of thermoregulation may also be associated with greater injury.MethodsIn the postnatal-day 7 (P7) rat, the effect of 5 h of graded hyperthermia (38 °C or 39 °C) immediately after unilateral HI was compared with normothermia (NT, 37 °C) and therapeutic hypothermia (TH, 32 °C). Early (negative geotaxis) and late (staircase test) behavioral testing was performed, as well as neuropathology scoring in adulthood. Separately, P7 rats were exposed to HI, and individual nesting temperatures were monitored before analysis of neuropathology at P14.ResultsMortality increased as temperature was increased from 38 °C (0%) to 39 °C (50%) after HI. Hyperthermia also resulted in early behavioral deficits compared with NT. In adulthood, pathology scores in the thalamus, basal ganglia, cortex, and hippocampus increased as post-hypoxic temperature increased above NT. Significant global neuroprotection was seen in the TH group. However, no significant difference was seen between HI groups in the staircase test. One hour after HI, the core temperature of pups was inversely correlated with global pathology scores at P14.ConclusionEarly temperature is a significant determinant of injury after experimental HI. Spontaneous decreases in core temperature after HI may confound neuroprotection studies.
authors.affiliation: Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wood
authors.affiliation: Department of Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hobbs
authors.affiliation: Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Falck
authors.affiliation: Department of Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Anne Charlotte
authors.initials: AC
authors.lastname: Brun
authors.affiliation: Department of Pathology at Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.affiliation: Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001831:Body Temperature; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006979:Hyperthermia, Induced; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000473:pathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000502:physiology*; D013997:Time Factors