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Prenatal Alcohol Exposure Affects Vasculature Development in the Neonatal Brain

Authors

  • Sylvie Jégou PhD,

    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
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  • Faiza El Ghazi PhD,

    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
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  • Pamela Kwetieu de Lendeu PhD,

    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
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  • Stéphane Marret MD, PhD,

    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
    2. Department of Neonatal Pediatrics and Intensive Care, Rouen University Hospital, Rouen
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  • Vincent Laudenbach MD, PhD,

    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
    2. Department of Neonatal Pediatrics and Intensive Care, Rouen University Hospital, Rouen
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  • Arnaud Uguen MD,

    1. Department of Pathology, Brest University Hospital, Brest
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  • Pascale Marcorelles MD, PhD,

    1. Department of Pathology, Brest University Hospital, Brest
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  • Vincent Roy PhD,

    1. Laboratory of Psychology and Neurosciences of Cognition and Affectivity, Rouen University, Rouen
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  • Annie Laquerrière MD, PhD,

    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
    2. Department of Pathology, Rouen University Hospital, Rouen, France
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  • Bruno José Gonzalez PhD

    Corresponding author
    1. Region-Inserm Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France
    • ERI28 “NeoVasc” 4309, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, Institute for Research and Innovation in Biomedicine, Normandy University, 76183 Rouen Cedex, France
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Abstract

Objective:

In humans, antenatal alcohol exposure elicits various developmental disorders, in particular in the brain. Numerous studies focus on the deleterious effects of alcohol on neural cells. Although recent studies suggest that alcohol can affect angiogenesis in adults, the impact of prenatal alcohol exposure on brain microvasculature remains poorly understood.

Methods:

We used a mouse model to investigate effects of prenatal alcohol exposure on the cortical microvascular network in vivo and ex vivo and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF) on activity, plasticity, and survival of microvessels. We used quantitative reverse transcriptase polymerase chain reaction, Western blot, immunohistochemistry, calcimetry, and videomicroscopy. We characterized the effect of prenatal alcohol exposure on the cortical microvascular network in human controls and fetal alcohol syndrome (FAS)/partial FAS (pFAS) patients at different developmental stages.

Results:

In mice, prenatal alcohol exposure induced a reduction of cortical vascular density, loss of the radial orientation of microvessels, and altered expression of VEGF receptors. Time-lapse experiments performed on brain slices revealed that ethanol inhibited glutamate-induced calcium mobilization in endothelial cells, affected plasticity, and promoted death of microvessels. These effects were prevented by VEGF. In humans, we evidenced a stage-dependent alteration of the vascular network in the cortices of fetuses with pFAS/FAS. Whereas no modification was observed from gestational week 20 (WG20) to WG22, the radial organization of cortical microvessels was clearly altered in pFAS/FAS patients from WG30 to WG38.

Interpretation:

Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol-induced brain abnormalities. Ann Neurol ANN NEUROL 2012;72:952–960

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