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

Alissa R. Carver, Maria Andrikopoulou, Jun Lei, Esther Tamayo, Phyllis Gamble, Zhipeng Hou, Jiangyang Zhang, Susumu Mori, George Saade, Maged Costantine, Irina Burd

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere100873
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 25 2014

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Pravastatin
Fetal Development
Brain
pre-eclampsia
animal models
Mothers
brain
Pre-Eclampsia
neocortex
Animals
Globus Pallidus
Animal Models
Neocortex
Magnetic resonance
magnetic resonance imaging
Magnetic Resonance Imaging
Imaging techniques
Inferior Colliculi
cytochemistry
Histocytochemistry

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Carver, A. R., Andrikopoulou, M., Lei, J., Tamayo, E., Gamble, P., Hou, Z., ... Burd, I. (2014). Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model. PLoS One, 9(6), [e100873]. https://doi.org/10.1371/journal.pone.0100873

Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model. / Carver, Alissa R.; Andrikopoulou, Maria; Lei, Jun; Tamayo, Esther; Gamble, Phyllis; Hou, Zhipeng; Zhang, Jiangyang; Mori, Susumu; Saade, George; Costantine, Maged; Burd, Irina.

In: PLoS One, Vol. 9, No. 6, e100873, 25.06.2014.

Research output: Contribution to journalArticle

Carver, AR, Andrikopoulou, M, Lei, J, Tamayo, E, Gamble, P, Hou, Z, Zhang, J, Mori, S, Saade, G, Costantine, M & Burd, I 2014, 'Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model', PLoS One, vol. 9, no. 6, e100873. https://doi.org/10.1371/journal.pone.0100873
Carver AR, Andrikopoulou M, Lei J, Tamayo E, Gamble P, Hou Z et al. Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model. PLoS One. 2014 Jun 25;9(6). e100873. https://doi.org/10.1371/journal.pone.0100873
Carver, Alissa R. ; Andrikopoulou, Maria ; Lei, Jun ; Tamayo, Esther ; Gamble, Phyllis ; Hou, Zhipeng ; Zhang, Jiangyang ; Mori, Susumu ; Saade, George ; Costantine, Maged ; Burd, Irina. / Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model. In: PLoS One. 2014 ; Vol. 9, No. 6.
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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.",
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AU - Carver, Alissa R.

AU - Andrikopoulou, Maria

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AU - Tamayo, Esther

AU - Gamble, Phyllis

AU - Hou, Zhipeng

AU - Zhang, Jiangyang

AU - Mori, Susumu

AU - Saade, George

AU - Costantine, Maged

AU - Burd, Irina

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N2 - 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.

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