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

 Fuente: PLoS One, 2014, 9(625), e100873

 Editorial: Public Library of Science

 Año de publicación: 2014

 Nº de páginas: 9

 Tipo de publicación: Artículo de Revista

 DOI: 10.1371/journal.pone.0100873

 ISSN: 1932-6203

 Url de la publicación: https://doi.org/10.1371/journal.pone.0100873

Autoría

CARVER, ALISSA R.

ANDRIKOPOULOU, MARIA

GAMBLE, PHYLLIS

HOU, ZHIPENG

ZHANG, JIANGYANG

MORI, SUSUMU

SAADE, GEORGE R.

COSTANTINE, MAGED M.

BURD, IRINA