Laura Pla1, Miriam Illa2,3, Carla Loreiro1,4, Mari Carmen Lopez1, Paula Vázquez-Aristizabal1, Britta Anna Kühne1,5, Marta Barenys5, Elisenda Eixarch1,4,6, Eduard Gratacós1,7,4,6. 1. BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, Barcelona, Spain. 2. BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Universitat de Barcelona, Barcelona, Spain, MIRIAMIL@clinic.cat. 3. Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain, MIRIAMIL@clinic.cat. 4. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 5. GRET, INSA-UB and Toxicology Unit, Pharmacology, Toxicology and Therapeutical Chemistry Department, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. 6. Center for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain. 7. Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain.
Abstract
BACKGROUND: Intrauterine growth restriction (IUGR) is associated with abnormal neurodevelopment, but the associated structural brain changes are poorly documented. The aim of this study was to describe in an animal model the brain changes at the cellular level in the gray and white matter induced by IUGR during the neonatal period. METHODS: The IUGR model was surgically induced in pregnant rabbits by ligating 40-50% of the uteroplacental vessels in 1 horn, whereas the uteroplacental vessels of the contralateral horn were not ligated. After 5 days, IUGR animals from the ligated horn and controls from the nonligated were delivered. On the day of delivery, perinatal data and placentas were collected. On postnatal day 1, functional changes were first evaluated, and thereafter, neuronal arborization in the frontal cortex and density of pre-oligodendrocytes, astrocytes, and microglia in the corpus callosum were evaluated. RESULTS: Higher stillbirth in IUGR fetuses together with a reduced birth weight as compared to controls was evidenced. IUGR animals showed poorer functional results, an altered neuronal arborization pattern, and a decrease in the pre-oligodendrocytes, with no differences in microglia and astrocyte densities. CONCLUSIONS: Overall, in the rabbit model used, IUGR is related to functional and brain changes evidenced already at birth, including changes in the neuronal arborization and abnormal oligodendrocyte maturation.
BACKGROUND: Intrauterine growth restriction (IUGR) is associated with abnormal neurodevelopment, but the associated structural brain changes are poorly documented. The aim of this study was to describe in an animal model the brain changes at the cellular level in the gray and white matter induced by IUGR during the neonatal period. METHODS: The IUGR model was surgically induced in pregnant rabbits by ligating 40-50% of the uteroplacental vessels in 1 horn, whereas the uteroplacental vessels of the contralateral horn were not ligated. After 5 days, IUGR animals from the ligated horn and controls from the nonligated were delivered. On the day of delivery, perinatal data and placentas were collected. On postnatal day 1, functional changes were first evaluated, and thereafter, neuronal arborization in the frontal cortex and density of pre-oligodendrocytes, astrocytes, and microglia in the corpus callosum were evaluated. RESULTS: Higher stillbirth in IUGR fetuses together with a reduced birth weight as compared to controls was evidenced. IUGR animals showed poorer functional results, an altered neuronal arborization pattern, and a decrease in the pre-oligodendrocytes, with no differences in microglia and astrocyte densities. CONCLUSIONS: Overall, in the rabbit model used, IUGR is related to functional and brain changes evidenced already at birth, including changes in the neuronal arborization and abnormal oligodendrocyte maturation.
Authors: Britta Anna Kühne; Paula Vázquez-Aristizabal; Mercè Fuentes-Amell; Laura Pla; Carla Loreiro; Jesús Gómez-Catalán; Eduard Gratacós; Miriam Illa; Marta Barenys Journal: Biomedicines Date: 2022-05-23
Authors: Laura Pla; Britta Anna Kühne; Laia Guardia-Escote; Paula Vázquez-Aristizabal; Carla Loreiro; Burkhard Flick; Eduard Gratacós; Marta Barenys; Miriam Illa Journal: Front Toxicol Date: 2022-07-22