title: Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model.
abstract: OBJECTIVE
  Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.
  
  
  METHODS
  For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group") or water (sFlt-1 "positive control") until weaning. The mFc group ("negative control") received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.
  
  
  RESULTS
  Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.
  
  
  CONCLUSIONS
  Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Alissa R
authors: AR
authors: Carver
authors: Integrated Research Center for Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Maria
authors: M
authors: Andrikopoulou
authors: Integrated Research Center for Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Jun
authors: J
authors: Lei
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Esther
authors: E
authors: Tamayo
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Phyllis
authors: P
authors: Gamble
authors: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Zhipeng
authors: Z
authors: Hou
authors: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Jiangyang
authors: J
authors: Zhang
authors: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Susumu
authors: S
authors: Mori
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: George R
authors: GR
authors: Saade
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Maged M
authors: MM
authors: Costantine
authors: Integrated Research Center for Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Irina
authors: I
authors: Burd
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001931:Brain Mapping; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D017035:Pravastatin / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin