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Effects of first trimester binge alcohol exposure on developing white matter in fetal sheep.

TitleEffects of first trimester binge alcohol exposure on developing white matter in fetal sheep.
Publication TypeJournal Article
Year of Publication2006
AuthorsWatari H, Born DE, Gleason CA
JournalPediatric research
Issue4 Pt 1
Date Published2006 Apr
KeywordsAlcohol Drinking, Animals, Body Weight, Brain, Ethanol, Female, Male, Gestational Age, Organ Size, Pregnancy, Pregnancy Trimester, First, Prenatal Exposure Delayed Effects, Sheep

<p>Heavy prenatal alcohol exposure is associated with neurodevelopmental abnormalities. Neuropathologic and neuroimaging studies have shown a wide range of structural problems, including abnormal neuronal migration and volume reduction in specific brain regions, including white matter. We identified foci of significant fetal white matter microglia-macrophage immunoreactivity in a &quot;binge&quot; model of early prenatal alcohol exposure in sheep. Ewes of alcohol-exposed fetuses received daily 90 min alcohol (1.5 gm/kg i.v.) infusions at 30-60 d gestation (term = 147 d). Ewes of control fetuses received same volume infusions of normal saline intravenously. Near-term (125 d gestation) fetal brains were labeled with microglia-macrophages using HAM56 antibody. We quantified dense immunoreactive cellular regions across sections and anatomical locations using computer-assisted microscopy and quantitative morphometry. The proportional HAM56-positive area in cortical white matter was greater in the alcohol-exposed fetuses (1.6%) compared with the saline controls (0.7%). The areas were localized to the frontal gyral white matter, temporal gyral white matter, optic radiation, and others (corpus callosum, septum pellucidum, fasciculus subcallosus, and external capsule), with a greater distribution in the gyral white matter. The greater area of macrophage-rich regions in near-term fetal sheep brain suggests a vulnerability of developing white matter that is enhanced by early alcohol exposure.</p>

Alternate JournalPediatr. Res.