title: Antenatal dexamethasone after asphyxia increases neural injury in preterm fetal sheep.
abstract: OBJECTIVE
  Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain.
  
  
  METHODS
  Chronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10) or saline (n = 10). Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach.
  
  
  RESULTS
  Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290 ± 76 vs 484 ± 98 neurons/mm(2), mean ± SEM, P<0.05) and basal ganglia (putamen, 538 ± 112 vs 814 ± 34 neurons/mm(2), P<0.05) compared to asphyxia-saline, and with greater loss of both total (913 ± 77 vs 1201 ± 75/mm(2), P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66 ± 8 vs 114 ± 12/mm(2), P<0.05, vs sham controls 165 ± 10/mm(2), P<0.001). This was associated with transient hyperglycemia (peak 3.5 ± 0.2 vs. 1.4 ± 0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum -1.5 ± 1.2 dB vs. -5.0 ± 1.4 dB in saline controls, P<0.01), but later onset and fewer overt seizures.
  
  
  CONCLUSIONS
  In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage.
authors.affiliation: Department of Physiology, the University of Auckland, Auckland New Zealand.
authors.forename: Miriam E
authors.initials: ME
authors.lastname: Koome
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Davidson
authors.forename: Paul P
authors.initials: PP
authors.lastname: Drury
authors.forename: Sam
authors.initials: S
authors.lastname: Mathai
authors.forename: Lindsea C
authors.initials: LC
authors.lastname: Booth
authors.forename: Alistair Jan
authors.initials: AJ
authors.lastname: Gunn
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001237:Asphyxia / Q000188:drug therapy / Q000473:pathology*; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D016923:Cell Death; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000009:adverse effects*; D004569:Electroencephalography; D005260:Female; D005333:Fetus; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007273:Injections, Intramuscular; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth / Q000473:pathology; D012756:Sheep; D034561:Sheep, Domestic; D014470:Umbilical Cord / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone