title: Prenatal alcohol exposure affects vasculature development in the neonatal brain.
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.
  
  
  CONCLUSIONS
  Prenatal alcohol exposure affects cortical angiogenesis both in mice and in pFAS/FAS patients, suggesting that vascular defects contribute to alcohol-induced brain abnormalities.
authors.affiliation: Region-INSERM Team, ERI28, Laboratory of Microvascular Endothelium and Neonate Brain Lesions, IRIB, Normandy University, Rouen, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jégou
authors.forename: Faiza
authors.initials: F
authors.lastname: El Ghazi
authors.forename: Pamela Kwetieu
authors.initials: PK
authors.lastname: de Lendeu
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudenbach
authors.forename: Arnaud
authors.initials: A
authors.lastname: Uguen
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Vincent
authors.initials: V
authors.lastname: Roy
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.forename: Bruno José
authors.initials: BJ
authors.lastname: Gonzalez
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D018826:CD13 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000473:pathology*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018715:Microscopy, Video; D055806:Microvessels / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D053580:Muscle Strength / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology* / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018826:CD13 Antigens; D002118:Calcium; D002492:Central Nervous System Depressants; D000431:Ethanol; D051272:Glucose Transporter Type 1; D018698:Glutamic Acid; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016194:Receptors, N-Methyl-D-Aspartate; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; C495677:SLC2A1 protein, human