1. Prenatal alcohol exposure affects vasculature development in the neonatal brain.
- Author
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Jégou S, El Ghazi F, de Lendeu PK, Marret S, Laudenbach V, Uguen A, Marcorelles P, Roy V, Laquerrière A, and Gonzalez BJ
- Subjects
- Age Factors, Animals, Animals, Newborn, CD13 Antigens metabolism, Calcium metabolism, Cell Death drug effects, Cerebral Cortex drug effects, Cerebral Cortex embryology, Cerebral Cortex growth & development, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, Endothelial Cells metabolism, Endothelial Cells pathology, Female, Fetal Alcohol Spectrum Disorders metabolism, Fetus, Gene Expression Regulation, Developmental drug effects, Glucose Transporter Type 1 genetics, Glucose Transporter Type 1 metabolism, Glutamic Acid pharmacology, Humans, In Vitro Techniques, Locomotion drug effects, Male, Maze Learning drug effects, Mice, Microscopy, Video, Microvessels metabolism, Muscle Strength physiology, Neovascularization, Pathologic pathology, Platelet Endothelial Cell Adhesion Molecule-1 genetics, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Pregnancy, Prenatal Exposure Delayed Effects physiopathology, Receptors, N-Methyl-D-Aspartate genetics, Receptors, N-Methyl-D-Aspartate metabolism, Receptors, Vascular Endothelial Growth Factor genetics, Receptors, Vascular Endothelial Growth Factor metabolism, Time Factors, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Central Nervous System Depressants adverse effects, Cerebral Cortex pathology, Ethanol adverse effects, Fetal Alcohol Spectrum Disorders pathology, Microvessels growth & development, Microvessels pathology, Prenatal Exposure Delayed Effects pathology
- 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., (Copyright © 2012 American Neurological Association.)
- Published
- 2012
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