PMID- 19860813 OWN - NLM STAT- MEDLINE DCOM- 20100810 LR - 20240317 IS - 1530-0277 (Electronic) IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 34 IP - 1 DP - 2010 Jan TI - Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7. PG - 98-111 LID - 10.1111/j.1530-0277.2009.01071.x [doi] AB - BACKGROUND: This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. METHODS: C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 microm isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. RESULTS: Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. CONCLUSIONS: Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development. FAU - Godin, Elizabeth A AU - Godin EA AD - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, USA. eamyers@med.unc.edu FAU - O'Leary-Moore, Shonagh K AU - O'Leary-Moore SK FAU - Khan, Amber A AU - Khan AA FAU - Parnell, Scott E AU - Parnell SE FAU - Ament, Jacob J AU - Ament JJ FAU - Dehart, Deborah B AU - Dehart DB FAU - Johnson, Brice W AU - Johnson BW FAU - Allan Johnson, G AU - Allan Johnson G FAU - Styner, Martin A AU - Styner MA FAU - Sulik, Kathleen K AU - Sulik KK LA - eng GR - P41 RR005959/RR/NCRR NIH HHS/United States GR - P60 AA011605/AA/NIAAA NIH HHS/United States GR - P50 AA011605/AA/NIAAA NIH HHS/United States GR - P30 HD003110/HD/NICHD NIH HHS/United States GR - AA017124/AA/NIAAA NIH HHS/United States GR - AA11605/AA/NIAAA NIH HHS/United States GR - AA007573/AA/NIAAA NIH HHS/United States GR - U24 CA092656/CA/NCI NIH HHS/United States GR - U01 AA017124/AA/NIAAA NIH HHS/United States GR - T32 AA007573/AA/NIAAA NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20091023 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 3K9958V90M (Ethanol) SB - IM MH - Age Factors MH - Animals MH - Brain/*abnormalities/*drug effects MH - Ethanol/*toxicity MH - Female MH - *Gestational Age MH - *Magnetic Resonance Imaging/methods MH - Mice MH - Mice, Inbred C57BL MH - Microscopy/methods MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced/pathology PMC - PMC3506027 MID - NIHMS408748 EDAT- 2009/10/29 06:00 MHDA- 2010/08/11 06:00 PMCR- 2012/11/26 CRDT- 2009/10/29 06:00 PHST- 2009/10/29 06:00 [entrez] PHST- 2009/10/29 06:00 [pubmed] PHST- 2010/08/11 06:00 [medline] PHST- 2012/11/26 00:00 [pmc-release] AID - ACER1071 [pii] AID - 10.1111/j.1530-0277.2009.01071.x [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2010 Jan;34(1):98-111. doi: 10.1111/j.1530-0277.2009.01071.x. Epub 2009 Oct 23.