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Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment. In this study, we hypothesized that repeated elevations in cortisol from chronic binge alcohol are responsible at least in part for fetal neuronal deficits. Animals were divided into four treatment groups: normal control, pair-fed saline control, alcohol and cortisol. The magnitude of elevation in cortisol in response to alcohol was mimicked in the cortisol group by infusing pregnant ewes with hydrocortisone for 6 h on each day of the experiment, and administering saline during the first hour in lieu of alcohol. The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109 until GD 132. Peak maternal blood alcohol concentration in the alcohol group was 239 ± 7 mg/dl. The fetal brains were collected and processed for stereological cell counting on GD 133. The estimated total number of fetal cerebellar Purkinje cells, the reference volume and the Purkinje cell density were not altered in response to glucocorticoid infusion in the absence of alcohol. These results suggest that glucocorticoids independently during the third trimester equivalent may not produce fetal cerebellar Purkinje cell loss. However, the elevations in cortisol along with other changes induced by alcohol could together lead to brain injury seen in the fetal alcohol spectrum disorders. Published by Elsevier Inc.

Citation

Shannon E Washburn, Ursula Tress, Emilie R Lunde, Wei-Jung A Chen, Timothy A Cudd. The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model. Alcohol (Fayetteville, N.Y.). 2013 Feb;47(1):53-61

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PMID: 23218665

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