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37: Maternal pravastatin therapy prevents altered brain development of the offspring in a murine model of preeclampsia

      Objective

      Using an animal model, we showed that preeclampsia alters brain candidate gene expression and results in long-term adverse neuromotor outcomes in the offspring, and this effect was prevented by antenatal treatment with pravastatin. This study aims to localize, by neuroimaging, the altered neuromotor programming in this animal model and the role of pravastatin in its prevention.

      Study Design

      At day 8 of gestation, pregnant CD-1 mice were randomized to tail vein injection with adenovirus carrying soluble Fms-like tyrosine kinase 1 (sFlt-1) or murine immunoglobulin G2Fc (mFc; control). sFlt-1 dams received pravastatin (5mg/kg/d; sFlt-pra group) or water (sFlt group) until weaning, and mFc received water (mFc group). Male offspring (representing 3-9 litters/group) at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using Brucker 11.7 Tesla horizontal bore MRI scanner. T2 and diffusion weighted images were acquired to evaluate the gross volumes of 29 regions of interest, including areas involved in the regulation of motor function (lateral globus pallidus, neocortex), spatial reasoning (fimbria, neocortex), sensory perception (neocortex), and adaptation to stress (stria medullaris) and pain (periaqueductal gray). 1-way ANOVA with multiple comparison testing was used for statistical analysis.

      Results

      Male sFlt-1 offspring showed decreased fimbria, periaquaductal gray, stria medullaris, and ventricular volume and increased lateral globus pallidus and neocortex volume (Figure 1: all p<0.05). Prenatal pravastatin treatment restored volumes to those seen in controls (p<0.05). Whole brain and cerebellar volumes were similar between groups.

      Conclusion

      Preeclampsia alters development in specific brain regions in adult offspring, and maternal therapy with pravastatin prevents this altered neuroanatomic programming in this animal model of preeclampsia.
      Figure thumbnail fx1
      Gross volume in mm3 for offspring brain regions which had significant loss of volume in the sFlt-1 group compared to mFc controls and pravastatin treatment group. Data presented as mean ± SEM.