An ontogeny study of cerebral vascular maturation in a sheep model of fetal growth restriction

Title: An ontogeny study of cerebral vascular maturation in a sheep model of fetal growth restriction Author, year: Elisa Lappalainen, 2018 Institution, city, country: Department of Physiology, Institution of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden AND The Ritchie Center, Hudson Institute of Medical Research, Clayton, Victoria, Australia Supervisors: Prof Carina Mallard, A/Prof Suzie Miller, Dr Margie Castillo-Melendez Background: In fetal growth restriction (FGR), the fetus fails to reach its genetically determined growth potential during gestation. It is most commonly caused by placental insufficiency that leads to chronic hypoxia in utero, affecting neurodevelopment. Aims: In this experimental ontogeny study, we aim to examine the expression and distribution of laminin, VEGF, MMP9, endoglin and Ki67 in the developing, growth-restricted ovine brains and compare the distribution to appropriately grown, gestational-age matched control animals. Methods: A growth restricted group and a control group of fetal sheep at 115, 125 and 145 (term) days of gestation were studied in this project. Sections of the periventricular white matter, subcortical white matter and subventricular zone were stained with immunohistochemistry. Results: The majority of the immunohistochemical markers used in this study showed no statistically significant differences between the FGR group and the control group at the gestational ages and the brain regions examined. Nonetheless, we found significant differences in the blood vessel 6 morphology parameters and blood vessel density between the gestational ages in several brain regions. We observed vascular expansion at 125 days of gestation. The total number of blood vessels appeared significantly increased in the white matter regions at term gestation compared to the earlier gestational ages regardless of growth restriction. The percentage of MMP9-positive blood vessels differed significantly between the gestational ages in the subcortical white matter of FGR and control animals. In the white matter regions, the results showed a trend of increased vascular proliferation in FGR and control animals at 115 and 125 days of gestation compared to term gestation. Conclusions: These results suggest a peak in vascular expansion at 125 days of gestation in FGR and control animals. This leads to increased number of blood vessels at term gestation in the white matter regions