Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model

• Published in: PloS one Vol. 9; no. 6; p. e100873
• Main Authors: Carver, Alissa R, Andrikopoulou, Maria, Lei, Jun, Tamayo, Esther, Gamble, Phyllis, Hou, Zhipeng, Zhang, Jiangyang, Mori, Susumu, Saade, George R, Costantine, Maged M, Burd, Irina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-06-2014; Public Library of Science (PLoS)
• Subjects: Adenoviruses; Anatomy; Animal models; Animals; Antilipemic agents; Biology and Life Sciences; Bore; Brain; Brain - cytology; Brain - drug effects; Brain - metabolism; Brain architecture; Brain Mapping; Brain research; Colliculus; Cytochemistry; Disease Models, Animal; Epigenetics; Female; Fetal Development - drug effects; Fetus - cytology; Fetus - drug effects; Fetus - metabolism; Fetuses; Fornix; Gender differences; Gene expression; Globus pallidus; Gynecology; Hypertension; Hypoxia; Image acquisition; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Immunoglobulins; Inferior colliculus; Laboratory animals; Magnetic resonance; Magnetic Resonance Imaging; Male; Males; Medicine; Medicine and Health Sciences; Mice; Neocortex; Neuroimaging; Obstetrics; Offspring; Pravastatin; Pravastatin - pharmacology; Pre-eclampsia; Pre-Eclampsia - metabolism; Pre-Eclampsia - pathology; Pre-Eclampsia - prevention & control; Preeclampsia; Pregnancy; Pregnant women; Progeny; Radiology; Rodents; Stains; Statins; Statistical analysis; Stria medullaris; Stroke; Systematic review; Thalamus; Tidal bores; Traumatic brain injury; Variance analysis; Vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Viruses; Weaning
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100873

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.
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.
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.
Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.