TY - JOUR
T1 - A mouse model of term chorioamnionitis
T2 - Unraveling causes of adverse neurological outcomes
AU - Burd, Irina
AU - Brown, Amy
AU - Gonzalez, Juan M.
AU - Chai, Jinghua
AU - Elovitz, Michal A.
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research and/or authorship of this article: supported by the NIH: 5-RO1-HD046544-0 (MAE) and supported part by the Institute for Translational Medicine and Therapeutics of the University of Pennsylvania. The project described was supported by Grand Number UL1RR024134 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
KW - chorioamnionitis
KW - delayed neurotoxicity
KW - mouse model of intrauterine inflammation
KW - neuroinflammation
KW - neuronal injury
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U2 - 10.1177/1933719111398498
DO - 10.1177/1933719111398498
M3 - Article
C2 - 21421895
AN - SCOPUS:80052009143
SN - 1933-7191
VL - 18
SP - 900
EP - 907
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 9
ER -