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Alcoholism Clinical and Experimental Research
Article . 2009 . Peer-reviewed
License: Wiley Online Library User Agreement
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UNC Dataverse
Article . 2009
Data sources: Datacite
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Magnetic Resonance Microscopy Defines Ethanol‐Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8

Authors: Shonagh K. O'Leary-Moore; Scott E. Parnell; Martin Styner; Kathleen K. Sulik; Brice W. Johnson; G. Allan Johnson; Elizabeth A. Godin; +1 Authors

Magnetic Resonance Microscopy Defines Ethanol‐Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8

Abstract

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 × 512 × 1024 image arrays were acquired using 3‐D spin warp encoding. The resulting 29 μm (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.

Keywords

Dose-Response Relationship, Drug, Ethanol, Abnormalities, Drug-Induced, Brain, Central Nervous System Depressants, Embryonic Development, Hippocampus, Magnetic Resonance Imaging, Olfactory Bulb, Mice, Inbred C57BL, Disease Models, Animal, Mice, Fetus, Fetal Alcohol Spectrum Disorders, Pregnancy, Cerebellum, Pituitary Gland, Animals, Female

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    citations
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    138
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
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    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
138
Top 10%
Top 10%
Top 1%
bronze