Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Placental growth factor (PGF) belongs to a family of proteins that promote blood vessel growth. It is abnormally low in the blood of women with preeclampsia, a hypertensive disorder of pregnancy. Children born to these preeclamptic pregnancies are known to have cognitive alterations. Preliminary data suggests that these children have brain structural and vascular differences compared to children born to unaffected pregnancies. Studies of mice lacking PGF have also shown brain structural and vascular differences compared to control mice leading us to question if low PGF during pregnancy could affect fetal brain development. The aim of our project is to confirm that PGF affects structural and vascular development of the brain by replacing the missing PGF in our mouse model. We hypothesize that this replacement will correct behavioural, brain structural and brain vascular deficits as compared to mice treated with saline. Mouse pups are injected with 10 pg/g PGF, 70 pg/g PGF, 700 pg/g PGF or saline from postnatal day 1 to postnatal day 10. These doses correspond to the physiological concentration of PGF present in non-pregnant mice, the concentration of PGF present in pregnant mice and a concentration of PGF ten times higher than found in mice. Behavioural testing is completed on the treated mice as adults. Subsequently, the mouse brains are imaged using magnetic resonance imaging to examine brain structures as well as micro-computed tomography imaging to examine the brain vasculature. Overall, the goal of our project is to further elucidate the role of PGF in brain development and determine if low PGF could be a possible factor in the altered cerebral development seen in children born to preeclamptic pregnancies.