Introduction: Maternal plasma in many pre-eclamptic (PE) pregnancies is low in the placenta product Placental growth factor (PGF). Offspring of PE compared to uncomplicated pregnancies show higher blood pressure, cognitive impairment and stroke; mechanisms explaining these differences are undefined. In Pgf−/− mice, decidual vessels have limited branching and connectivity. We asked if PGF deficiency diminishes brain vascular development, impairs cognition and elevates stroke risk.
Materials and Methods: Pgf−/− and Pgf+/+ brain vasculatures were compared by resin casts (adults) or whole-mount immunohistochemistry (gestation day (GD) 10.5 fetal hindbrains). In adults, cognitive functions were compared by the tail-suspension test (TST) and Y-maze alternation test (YMAT) and 30 min left common carotid artery occlusion was used to compare stroke susceptibility. Brains were recovered, stained with 2,3,5-triphenyltetrazolium chloride (TTC) to identify ischemic regions or processed for RNA collection and qRT-PCR analyses.
Results and Discussion: Adult Pgf−/− brain arteries were less connected than in controls often showing an incomplete Circle of Willis. Fetal Pgf−/− hindbrain vessels were less mature and more disorganized than in controls. Pgf−/− were twice as depressed (TST) and had 50% less spatial learning ability (YMAT) than Pgf+/+. Large brain infarcts were detected in all Pgf−/− mice after occlusion while controls lacked infarcts. Thus, PGF is essential for normal fetal cerebral vasculogenesis and normal adult brain perfusion and cognitive functioning. In PE, PGF may be deficient in the fetal as well as placental compartment leading to disturbed brain vascular development that elevates stroke risk and impairs cognitive functioning.
Funding: NSERC, CIHR and CRC programs.
02 Sep 2014 - 04 Sep 2014