%0 Journal Article
%T Antenatal Dexamethasone after Asphyxia Increases Neural Injury in Preterm Fetal Sheep
%A Miriam E. Koome
%A Joanne O. Davidson
%A Paul P. Drury
%A Sam Mathai
%A Lindsea C. Booth
%A Alistair Jan Gunn
%A Laura Bennet
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0077480
%X Background and Purpose 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¡À76 vs 484¡À98 neurons/mm2, mean¡ÀSEM, P<0.05) and basal ganglia (putamen, 538¡À112 vs 814¡À34 neurons/mm2, P<0.05) compared to asphyxia-saline, and with greater loss of both total (913¡À77 vs 1201¡À75/mm2, P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66¡À8 vs 114¡À12/mm2, P<0.05, vs sham controls 165¡À10/mm2, P<0.001). This was associated with transient hyperglycemia (peak 3.5¡À0.2 vs. 1.4¡À0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum £¿1.5¡À1.2 dB vs. £¿5.0¡À1.4 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077480