Journal article
Chorioamnionitis induces enteric nervous system injury: Effects of timing and inflammation in the ovine fetus
Molecular Medicine, Vol.26(1), Art. 82
2020
Abstract
Background
Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model.
Methods
We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days.
Results
Four days of IA LPS exposure causes a decreased PGP9.5- and S100β-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure.
Conclusions
The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies.
Details
- Title
- Chorioamnionitis induces enteric nervous system injury: Effects of timing and inflammation in the ovine fetus
- Authors/Creators
- C. Heymans (Author/Creator) - Maastricht UniversityI.H. de Lange (Author/Creator) - University College MaastrichtK. Lenaerts (Author/Creator) - Maastricht UniversityL.C.G.A. Kessels (Author/Creator)M. Hadfoune (Author/Creator) - Maastricht UniversityG. Rademakers (Author/Creator) - Maastricht UniversityV. Melotte (Author/Creator) - Maastricht UniversityW. Boesmans (Author/Creator) - Hasselt UniversityB.W. Kramer (Author/Creator) - University College MaastrichtA.H. Jobe (Author/Creator) - Cincinnati Children's Hospital Medical CenterM. Saito (Author/Creator) - Tohoku University HospitalM.W. Kemp (Author/Creator) - The University of Western AustraliaW.G. van Gemert (Author/Creator) - Maastricht UniversityT.G.A.M. Wolfs (Author/Creator) - University College Maastricht
- Publication Details
- Molecular Medicine, Vol.26(1), Art. 82
- Publisher
- BioMed Central as part of Springer Nature
- Identifiers
- 991005541495207891
- Copyright
- © 2020 The Author(s)
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.195 Neuroendocrine & Intestinal Disorders
- 1.195.1341 Enteric Nervous System
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Medicine, Research & Experimental
- ESI research areas
- Molecular Biology & Genetics