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Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8.

Publication ,  Journal Article
Parnell, SE; O'Leary-Moore, SK; Godin, EA; Dehart, DB; Johnson, BW; Allan Johnson, G; Styner, MA; Sulik, KK
Published in: Alcohol Clin Exp Res
June 2009

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.

Duke Scholars

Published In

Alcohol Clin Exp Res

DOI

EISSN

1530-0277

Publication Date

June 2009

Volume

33

Issue

6

Start / End Page

1001 / 1011

Location

England

Related Subject Headings

  • Substance Abuse
  • Pregnancy
  • Pituitary Gland
  • Olfactory Bulb
  • Mice, Inbred C57BL
  • Mice
  • Magnetic Resonance Imaging
  • Hippocampus
  • Fetus
  • Fetal Alcohol Spectrum Disorders
 

Citation

APA
Chicago
ICMJE
MLA
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Parnell, S. E., O’Leary-Moore, S. K., Godin, E. A., Dehart, D. B., Johnson, B. W., Allan Johnson, G., … Sulik, K. K. (2009). Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8. Alcohol Clin Exp Res, 33(6), 1001–1011. https://doi.org/10.1111/j.1530-0277.2009.00921.x
Parnell, Scott E., Shonagh K. O’Leary-Moore, Elizabeth A. Godin, 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 8.Alcohol Clin Exp Res 33, no. 6 (June 2009): 1001–11. https://doi.org/10.1111/j.1530-0277.2009.00921.x.
Parnell SE, O’Leary-Moore SK, Godin EA, Dehart DB, Johnson BW, Allan Johnson G, et al. Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8. Alcohol Clin Exp Res. 2009 Jun;33(6):1001–11.
Parnell, Scott E., et al. “Magnetic resonance microscopy defines ethanol-induced brain abnormalities in prenatal mice: effects of acute insult on gestational day 8.Alcohol Clin Exp Res, vol. 33, no. 6, June 2009, pp. 1001–11. Pubmed, doi:10.1111/j.1530-0277.2009.00921.x.
Parnell SE, O’Leary-Moore SK, Godin EA, 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 8. Alcohol Clin Exp Res. 2009 Jun;33(6):1001–1011.
Journal cover image

Published In

Alcohol Clin Exp Res

DOI

EISSN

1530-0277

Publication Date

June 2009

Volume

33

Issue

6

Start / End Page

1001 / 1011

Location

England

Related Subject Headings

  • Substance Abuse
  • Pregnancy
  • Pituitary Gland
  • Olfactory Bulb
  • Mice, Inbred C57BL
  • Mice
  • Magnetic Resonance Imaging
  • Hippocampus
  • Fetus
  • Fetal Alcohol Spectrum Disorders