title: Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus.
abstract: Postoperative ileus (POI) is characterized by a transient inhibition of gastrointestinal (GI) motility after abdominal surgery mediated by the inflammation of the muscularis externa (ME). The aim of this study was to identify alterations in the enteric nervous system that may contribute to the pathogenesis of POI.
  
  
  
  Gastrointestinal transit, contractility of isolated smooth muscle strips and inflammatory parameters were evaluated at different time points (1.5 h to 10 days) after intestinal manipulation (IM) in mice. Immune-labeling was used to visualize changes in myenteric neurons.
  
  
  
  Intestinal manipulation resulted in an immediate inhibition of GI transit recovering between 24 h and 5 days. In vitro contractility to K(+) (60 mM) or carbachol (10(-9) to 10(-4) M) was biphasically suppressed over 24 h after IM (with transient recovery at 6 h). The first phase of impaired myogenic contractility was associated with increased expression of TNF-α, IL-6 and IL-1α. After 24 h, we identified a significant reduction in electrical field stimulation-evoked contractions and relaxations, lasting up to 10 days after IM. This was associated with a reduced expression of chat and nos1 genes.
  
  
  
  Intestinal manipulation induces two waves of smooth muscle inhibition, most likely mediated by inflammatory cytokines, lasting up to 3 days after IM. Further, we here identify a late third phase (>24 h) characterized by impaired cholinergic and nitrergic neurotransmission persisting after recovery of muscle contractility. These findings illustrate that POI results from inflammation-mediated impaired smooth muscle contraction, but also involves a long-lasting impact of IM on the enteric nervous system.
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Farro
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: P J
authors.initials: PJ
authors.lastname: Gomez-Pinilla
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Di Giovangiulio
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Stakenborg
authors.affiliation: Division of Physiology, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Auteri
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Thijs
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Depoortere
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Matteoli
authors.affiliation: Division of Gastroenterology, Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: G E
authors.initials: GE
authors.lastname: Boeckxstaens
mesh_terms: D000818:Animals; D017615:Enteric Nervous System / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D045823:Ileus / Q000378:metabolism / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology*; D009924:Organ Culture Techniques; D011183:Postoperative Complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018836:Inflammation Mediators
keywords: enteric neurons; inflammation; intestinal motility; postoperative ileus