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A Mouse Model of Term Chorioamnionitis Unraveling Causes of Adverse Neurological Outcomes

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Abstract

Maternal fever and/or chorioamnionitis at term are associated with an increased prevalence of adverse neurobehavioral outcomes in exposed offspring. Since the mechanisms of such injury are currently unknown, the objectives of this study were to elucidate whether intrauterine inflammation at term results in fetal brain injury. Specifically, we assessed brain injury by investigating the cytokine response, white matter damage, and neuronal injury and viability. A mouse model of intrauterine inflammation at term was utilized by injecting lipopolysaccharide (LPS), or normal saline into uterine horn. Compared to saline-exposed, LPS-exposed fetal brains had significantly increased IL-1β and IL-6 messenger RNA (mRNA) expression (P < .05 for both) and IL-6 protein levels by enzyme-linked immunosorbent assay (ELISA;P < 0.05). Fetal neurons were affected by the intrauterine and fetal brain inflammation, as demonstrated by significantly decreased microtubule-associated protein 2 (MAP2) mRNA expression and a decrease in immunocytochemical staining (a marker of neuronal cytoskeleton development;P < .05), altered neuronal morphology (P < 0.05), and delayed neurotoxicity (P < .05). These fetal neuronal changes occurred without overt changes in white matter damage markers. Marker of astrocyte development and astrogliosis (glial fibrillary acidic protein [GFAP]) did not show an increase; pro-oligodendrocyte marker (PLP1/DM20) was not significantly changed (P > .05). These studies may provide a critical mechanism for the observed long-term adverse neurobehavioral outcomes after exposure to chorioamnionitis at term.

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Authors and Affiliations

  1. Maternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, University of Pennsylvania, 1352 Biomedical Research Building II/III, 421 Curie Boulevard, 19104, PA, Philadelphia, USA

    Irina Burd MD, PhD, Amy Brown PhD, Juan M. Gonzalez MD, Jinghua Chai MD & Michal A. Elovitz MD

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  1. Irina Burd MD, PhD
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  2. Amy Brown PhD
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  3. Juan M. Gonzalez MD
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  4. Jinghua Chai MD
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  5. Michal A. Elovitz MD
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Burd, I., Brown, A., Gonzalez, J.M. et al. A Mouse Model of Term Chorioamnionitis Unraveling Causes of Adverse Neurological Outcomes. Reprod. Sci. 18, 900–907 (2011). https://doi.org/10.1177/1933719111398498

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  • DOI: https://doi.org/10.1177/1933719111398498

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