Vagal Innervation and Early Postoperative Ileus in Mice

Mueller, Mario H.; Karpitschka, M.; Gao, Zhen; Mittler, Sarah; Kasparek, Michael S.; Renz, Bernhard W.; Sibaev, Andrei; Glatzle, Jörg; Li, Yongyu; Kreis, Martin E.

doi:10.1007/s11605-011-1481-2

Cited by 12 publications

(26 citation statements)

References 25 publications

(40 reference statements)

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“…Kalff et al [8] demonstrated the increased mRNA and protein expression of intercellular adhesion molecule 1 (ICAM-1) and p-selectin in the intestinal muscularis of POI, and the introduction of ICAM-1 antibody may prevent the aggregation of monocytes and neutrophils in the intestinal muscularis and ameliorate the functional disorder of jejunum circular muscle during POI. In the previous work, we confirmed this inflammatory response in the intestinal muscularis, and showed elevated myeloperoxidase (MPO) activity indicating increased numbers of neutrophils during POI [9]. All of these studies explored the role of inflammatory responses in POI at its early stage, few hours after the surgical operations [10].…”

Section: Introductionsupporting

confidence: 55%

“…Specifically, POI is characterized by infiltration of leukocytes in the gut wall 24 h after surgery, and the majority of these cells are macrophages [7], [10], [28]. In this study, the method we used to induce postoperative ileus in mice is by mechanical intestinal manipulation which is an extremely well-established model world-wide [9], [29], [30]. However, it needs to be controlled by group size and standardized use under defined circumstances, to avoid the variability in experimental groups.…”

Section: Discussionmentioning

confidence: 99%

“…According to previously published procedures [9], postoperative ileus was induced. In brief, under enflurane anesthesia, animals were laparotomized and followed by sham treatment or standardized small bowel manipulation.…”

Section: Methodsmentioning

confidence: 99%

“…Myeloperoxidase (MPO) staining: as described previously [9], staining of MPO-positive cells was performed by incubating whole mounts in a mixture of 10 mg Hankers-Yates reagent, 10 ml Krebs-Ringer buffer, and 100 μL 3% hydrogen peroxidase for 10 minutes. To quantify FITC avidin positive cells or F4/80 staining, a fluorescent microscope (Axiophot, Zeiss, Feldbach, Switzerland) was used at a 400 fold magnification.…”

Section: Methodsmentioning

confidence: 99%

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The Dual Effect of Cannabinoid Receptor-1 Deficiency on the Murine Postoperative Ileus

Cao

Goetz

et al. 2013

PLoS ONE

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IntroductionIntestinal inflammatory responses play a critical role in the pathogenesis of postoperative ileus (POI). As cannabinoid receptor-1 (CB1) is involved in inhibiting gastrointestinal (GI) motility and anti-inflammation, we aimed to explore its contribution to POI.MethodsExperimental POI was induced in adult female CB1-deficient (CB1–/–) mice and wild-type littermates (C57BL/6N) by standardized small bowel manipulation. Twenty-four hours after surgery, GI transit was assessed by charcoal transport. FITC avidin, F4/80, and myeloperoxidase immunohistochemistry techniques were used to evaluate the inflammatory response in the muscularis of ileum and colon. Expressions of p38MAPK and its phosphorylated form (pp38) in the intestine were determined. Plasma levels of proinflammatory cytokines and chemokines were measured by ELISA as well.ResultsPOI was characterized by decreased GI transit (p<0.01) and accompanied by a marked intestinal and systematic inflammatory response in wild-type and CB1–/– mice. Increased numbers of inflammatory cells, including macrophages, neutrophils, and mast cells were observed in the muscularis of ileum and colon (p<0.01, or p<0.05). Plasma levels of interleukin-6 (IL-6), cytokine-induced neutrophil chemoattractant-1 (CINC-1/KC), and monocyte chemoattractant protein-1 (MCP-1) were elevated (p<0.01, or p<0.05). Expression of p38 and pp38 increased in the intestine (p<0.01, or p<0.05). CB1–/– mice showed an increased inflammatory response during POI, especially the systemic inflammatory markers, such as IL-6, KC, CINC1, and pp38 expression were increased as compared to those in WT mice (p<0.05).ConclusionsIntestinal motility was inhibited during POI. In this condition, inhibition of motility did not seem to be altered by the absence of CB1 receptors, however, an increased inflammatory response was observed in CB1–/– mice. Hence, CB1 receptor activation rather than inhibition may reduce the inflammatory response in POI, which has a remote potential to relate into reduced inhibition of intestinal motility during POI.

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Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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The Dual Effect of Cannabinoid Receptor-1 Deficiency on the Murine Postoperative Ileus

Cao

Goetz

et al. 2013

PLoS ONE

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“…However, these authors, unlike us, could not show increased myeloperoxidase-positive infiltrates in the unmanipulated colon (15). In contrast, Mueller et al could show that vagal inhibition of the intestinal immune response is present at 9 h but not detectable earlier after IM (56). All in all, although the improved gastrointestinal and CT might be explained by an altered immunological activity, our findings do not exclude the contribution of neuronal signals to the postoperative ileus (2,14,42).…”

Section: Discussioncontrasting

confidence: 99%

The role of lymphoid tissue in the attenuation of the postoperative ileus

Koscielny

Engel

Maurer

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune-mediated. The aim of this study was to investigate the role of secondary lymphoid organs [mesenteric lymph nodes (MLN), gut-associated lymphoid tissue (GALT)] in IM-mediated FE by employing mice with deficient secondary lymphoid organs (aly/aly, MLN ex) or by administration of 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol (FTY720), an immunomodulating agent that inhibits emigration of lymphocytes out of lymphoid organs. Small bowel muscularis, and colonic muscularis from wild-type mice as control, from aly/aly mice, FTY720-treated mice (daily dose of 1.0 mg/kg mouse ip starting 3 days before surgical procedure), and wild-type mice that had undergone removal of mesenteric lymph nodes before IM (MLN ex mice) were obtained after selective IM of the jejunum or sham operation. FE was analyzed by measuring transit time of orally administered fluorescent dextran in the gastrointestinal tract [geometric center (GC) of fluorescent dextran], colonic transit time, infiltration of myeloperoxidase-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α] were determined by Taqman-PCR. We observed a significantly reduced upregulation of proinflammatory cytokines (IL-6, TNF-α, MIP-1α) in colonic muscularis of MLN ex mice, aly/aly mice, and FTY720-treated mice compared with wild-type mice. Contractility of circular muscularis strips of the colon but not the jejunum was significantly improved in aly/aly mice and FTY720-treated wild-type mice. Additionally, inflammation of the colon determined by the number of myeloperoxidase-positive cells and colonic transit time were significantly improved in aly/aly mice, FTY720-treated wild-type mice, and in MLN ex mice. In summary, lack of secondary lymphoid organs (MLN + GALT) in aly/aly mice or administration of FTY720 abrogated FE after IM as opposed to wild-type mice. These data demonstrate that secondary lymphoid organs are involved in the propagation of FE and postoperative ileus. FTY720 indirectly affects FE by inhibiting migration of activated T cells from the jejunum and adjacent secondary lymphoid organs to the colon. These findings support the crucial role of the adaptive immune system in FE, most likely by a sphyngosine 1-phosphate-dependent mechanism.

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Postoperative Ileus: Prevention and Treatment

Adiamah

Lobo

2020

Enhanced Recovery After Surgery

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Vagal Innervation and Early Postoperative Ileus in Mice

Cited by 12 publications

References 25 publications

The Dual Effect of Cannabinoid Receptor-1 Deficiency on the Murine Postoperative Ileus

The Dual Effect of Cannabinoid Receptor-1 Deficiency on the Murine Postoperative Ileus

The role of lymphoid tissue in the attenuation of the postoperative ileus

Postoperative Ileus: Prevention and Treatment

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