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

Overview

Journal Reprod Sci

Publisher Springer

Specialty Reproductive Medicine

Date 2011 Mar 23

PMID 21421895

Citations 41

Authors

Irina Burd

Amy Brown

Juan M Gonzalez

Jinghua Chai

Michal A Elovitz

Affiliations

Soon will be listed here.

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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