title: Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.
abstract: Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lear
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Davidson
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Georgia R
authors.initials: GR
authors.lastname: Mackay
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Drury
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Robert
authors.initials: R
authors.lastname: Galinsky
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Josine S
authors.initials: JS
authors.lastname: Quaedackers
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
mesh_terms: D000818:Animals; D001238:Asphyxia Neonatorum / Q000473:pathology*; D001921:Brain / Q000473:pathology; D003907:Dexamethasone / Q000633:toxicity*; D004569:Electroencephalography; D005260:Female; D005333:Fetus / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006943:Hyperglycemia / Q000139:chemically induced* / Q000473:pathology*; D007969:Leukomalacia, Periventricular / Q000139:chemically induced* / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D007752:Obstetric Labor, Premature; D011247:Pregnancy; D012640:Seizures / Q000209:etiology; D012756:Sheep; D014470:Umbilical Cord
chemical_list: D003907:Dexamethasone; D005947:Glucose
keywords: Glucocorticoids; asphyxia; hyperglycemia; periventricular leukomalacia; premature birth