title: Effects of antenatal uteroplacental hypoperfusion on neonatal microvascularisation and excitotoxin sensitivity in mice.
abstract: Vascular intrauterine growth restriction (IUGR) occurs in about 5% of pregnancies and may reduce the incidence of periventricular leukomalacia in preterm newborns. We evaluated neonatal excitotoxicity in a murine model of vascular IUGR involving unilateral uterine ligation on embryonic day (E)13.5. Birth weight was significantly decreased in the ligation group compared with the sham group (p < 0.001). VEGFs, VEGF receptors (VEGFRs), and NMDA receptor subunit mRNAs in brain extracts were assayed using quantitative RT-PCR. Ligation was associated with increased mRNAs for the vascular marker PECAM-1 on postnatal day (PD)2 and VEGFR-3 on PD2 and PD10, contrasting with decreased VEGFA and VEGFC on PD10. Microvessel density was increased on PD7. Ligated and sham pups received intracerebral ibotenate (NMDA agonist) on PD2 or PD10. Cortical and white matter (WM) lesions after 5 d were reduced in ligated versus sham pups injected on PD2 (p < 0.001 and p < 0.01, respectively); this effect persisted on PD42 (p < 0.01 and p < 0.05, respectively). With ibotenate on PD10, lesions were exacerbated after 5 d in the ligated group in the cortex (p < 0.05) and WM (p < 0.05) and on PD42 in the cortex (p < 0.05). In conclusion, vascular IUGR offered only transient protection against neonatal excitotoxic lesions, possibly via angiogenesis.
authors.affiliation: Normandy-Rouen University Institute for Biomedical Research, IFRMP23, 76183 Rouen, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Catteau
authors.forename: Jaine-Iscia
authors.initials: JI
authors.lastname: Gernet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.forename: Hélène
authors.initials: H
authors.lastname: Legros
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Philippe
authors.initials: P
authors.lastname: Leroux
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudenbach
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005317:Fetal Growth Retardation; D006801:Humans; D007051:Ibotenic Acid / Q000494:pharmacology / Q000633:toxicity; D007511:Ischemia / Q000503:physiopathology*; D051379:Mice; D008833:Microcirculation; D009498:Neurotoxins / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016194:Receptors, N-Methyl-D-Aspartate; D042461:Vascular Endothelial Growth Factor A; D007051:Ibotenic Acid; D040262:Receptors, Vascular Endothelial Growth Factor