Effects of first trimester binge alcohol exposure on developing white matter in fetal sheep.
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 "binge" 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.
Department of Pathology-Neuropathology, University of Washington, Seattle, Washington 98195, USA.
Hirofumi
H
Watari
Donald E
DE
Born
Christine A
CA
Gleason
D000428:Alcohol Drinking; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000196:embryology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep
D000431:Ethanol