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.
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Abbreviations
- AUVL:
-
antenatal uterine vessel ligation
- E:
-
embryonic day
- i.c.:
-
intracerebral
- NMDA-R:
-
glutamate receptors of the N-methyl-d-aspartic acid type
- PD:
-
postnatal day
- PECAM-1:
-
platelet endothelial cell adhesion molecule-1, CD-31
- PVL:
-
periventricular leukomalacia
- VEGFR:
-
VEGF receptors (types 1, 2 or 3)
- WM:
-
white matter
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Acknowledgements
We thank Dr. S. Jegou-Colleter, Dr. B.J. Gonzalez, and Dr. P. Mulder for technical help and critical discussion.
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Supported by University of Rouen, the Institut National de la Santé et de la Recherche Médicale (INSERM), the Société Française d'Anesthésie Réanimation (SFAR), ELA Foundation, the European Found for Regional Development (FEDER), the Regional Council of Haute-Normandie, and the National Research Agency (ANR).
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Catteau, J., Gernet, JI., Marret, S. et al. Effects of Antenatal Uteroplacental Hypoperfusion on Neonatal Microvascularisation and Excitotoxin Sensitivity in Mice. Pediatr Res 70, 229–235 (2011). https://doi.org/10.1203/PDR.0b013e318224285f
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DOI: https://doi.org/10.1203/PDR.0b013e318224285f
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