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Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7.

Publication ,  Journal Article
Godin, EA; O'Leary-Moore, SK; Khan, AA; Parnell, SE; Ament, JJ; Dehart, DB; Johnson, BW; Allan Johnson, G; Styner, MA; Sulik, KK
Published in: Alcohol Clin Exp Res
January 2010

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.

Duke Scholars

Published In

Alcohol Clin Exp Res

DOI

EISSN

1530-0277

Publication Date

January 2010

Volume

34

Issue

1

Start / End Page

98 / 111

Location

England

Related Subject Headings

  • Substance Abuse
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Microscopy
  • Mice, Inbred C57BL
  • Mice
  • Magnetic Resonance Imaging
  • Gestational Age
  • Female
  • Ethanol
 

Citation

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Chicago
ICMJE
MLA
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Godin, E. A., O’Leary-Moore, S. K., Khan, A. A., Parnell, S. E., Ament, J. J., Dehart, D. B., … Sulik, K. K. (2010). Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7. Alcohol Clin Exp Res, 34(1), 98–111. https://doi.org/10.1111/j.1530-0277.2009.01071.x
Godin, Elizabeth A., Shonagh K. O’Leary-Moore, Amber A. Khan, Scott E. Parnell, Jacob J. Ament, Deborah B. Dehart, Brice W. Johnson, G. Allan Johnson, Martin A. Styner, and Kathleen K. Sulik. “Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7.Alcohol Clin Exp Res 34, no. 1 (January 2010): 98–111. https://doi.org/10.1111/j.1530-0277.2009.01071.x.
Godin EA, O’Leary-Moore SK, Khan AA, Parnell SE, Ament JJ, Dehart DB, et al. Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7. Alcohol Clin Exp Res. 2010 Jan;34(1):98–111.
Godin, Elizabeth A., et al. “Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7.Alcohol Clin Exp Res, vol. 34, no. 1, Jan. 2010, pp. 98–111. Pubmed, doi:10.1111/j.1530-0277.2009.01071.x.
Godin EA, O’Leary-Moore SK, Khan AA, Parnell SE, Ament JJ, Dehart DB, Johnson BW, Allan Johnson G, Styner MA, Sulik KK. Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 7. Alcohol Clin Exp Res. 2010 Jan;34(1):98–111.
Journal cover image

Published In

Alcohol Clin Exp Res

DOI

EISSN

1530-0277

Publication Date

January 2010

Volume

34

Issue

1

Start / End Page

98 / 111

Location

England

Related Subject Headings

  • Substance Abuse
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Microscopy
  • Mice, Inbred C57BL
  • Mice
  • Magnetic Resonance Imaging
  • Gestational Age
  • Female
  • Ethanol