PMID- 19302087 OWN - NLM STAT- MEDLINE DCOM- 20090907 LR - 20240312 IS - 1530-0277 (Electronic) IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 33 IP - 6 DP - 2009 Jun TI - Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8. PG - 1001-11 LID - 10.1111/j.1530-0277.2009.00921.x [doi] AB - BACKGROUND: Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol's insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM-based atlas of developmental stage-dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. METHODS: For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin's/Prohance solution. Control fetuses from vehicle-treated dams were stage-matched to those that were ethanol-exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 x 512 x 1024 image arrays were acquired using 3-D spin warp encoding. The resulting 29 microm (isotropic) resolution images were processed using ITK-SNAP, a 3-D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. RESULTS: As compared with controls, the crown-rump lengths of stage-matched ethanol-exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. CONCLUSIONS: This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages. FAU - Parnell, Scott E AU - Parnell SE AD - The Bowles Center for Alcohol Studies, and Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, NC 27599-7178, USA. sparnell@med.unc.edu FAU - O'Leary-Moore, Shonagh K AU - O'Leary-Moore SK FAU - Godin, Elizabeth A AU - Godin EA 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 - U01 AA 017124/AA/NIAAA NIH HHS/United States GR - HD 03110/HD/NICHD NIH HHS/United States GR - P41 RR005959/RR/NCRR NIH HHS/United States GR - U24 CA092656/CA/NCI NIH HHS/United States GR - P60 AA011605/AA/NIAAA NIH HHS/United States GR - U24 CA 092656/CA/NCI NIH HHS/United States GR - P41 RR005959-19/RR/NCRR NIH HHS/United States GR - AA 11605/AA/NIAAA NIH HHS/United States GR - P50 AA011605/AA/NIAAA NIH HHS/United States GR - U01 AA017124/AA/NIAAA NIH HHS/United States GR - P60 AA011605-060004/AA/NIAAA NIH HHS/United States GR - P41 CA 05959/CA/NCI NIH HHS/United States GR - U24 CA092656-08/CA/NCI NIH HHS/United States GR - P30 HD003110/HD/NICHD NIH HHS/United States GR - U01 AA017124-03/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090319 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 0 (Central Nervous System Depressants) RN - 3K9958V90M (Ethanol) SB - IM MH - *Abnormalities, Drug-Induced MH - Animals MH - Brain/*abnormalities/drug effects/*embryology MH - Central Nervous System Depressants/*toxicity MH - Cerebellum/abnormalities/drug effects/embryology MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Embryonic Development/drug effects MH - Ethanol/*toxicity MH - Female MH - Fetal Alcohol Spectrum Disorders/*pathology MH - Fetus/*drug effects/pathology MH - Hippocampus/abnormalities/drug effects/embryology MH - Magnetic Resonance Imaging MH - Mice MH - Mice, Inbred C57BL MH - Olfactory Bulb/abnormalities/drug effects/embryology MH - Pituitary Gland/abnormalities/drug effects/embryology MH - Pregnancy PMC - PMC2748865 MID - NIHMS145920 EDAT- 2009/03/24 09:00 MHDA- 2009/09/08 06:00 PMCR- 2010/06/01 CRDT- 2009/03/24 09:00 PHST- 2009/03/24 09:00 [entrez] PHST- 2009/03/24 09:00 [pubmed] PHST- 2009/09/08 06:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - ACER921 [pii] AID - 10.1111/j.1530-0277.2009.00921.x [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2009 Jun;33(6):1001-11. doi: 10.1111/j.1530-0277.2009.00921.x. Epub 2009 Mar 19.