Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon

Universität Mannheim, Mannheim, Baden-Württemberg, Germany
Gastroenterology (Impact Factor: 13.93). 11/2002; 123(5):1459-67. DOI: 10.1053/gast.2002.36600
Source: PubMed

ABSTRACT A variety of gastrointestinal motility disorders have been attributed to alterations of interstitial cells of Cajal and malformations of the enteric nervous system. This study evaluates both the distribution of interstitial cells of Cajal and the pathohistology of the enteric nervous system in 2 severe human colorectal motility disorders.
Colonic specimens obtained from patients with slow-transit constipation (n = 11), patients with megacolon (n = 6), and a control group (n = 13, nonobstructing neoplasia) were stained with antibodies against c-kit (marker for interstitial cells of Cajal) and protein gene product 9.5 (neuronal marker). The morphometric analysis of interstitial cells of Cajal included the separate registration of the number and process length within the different regions of the muscularis propria. The structural architecture of the enteric nervous system was assessed on microdissected whole-mount preparations.
In patients with slow-transit constipation, the number of interstitial cells of Cajal was significantly decreased in all layers except the outer longitudinal muscle layer. The myenteric plexus showed a reduced ganglionic density and size (moderate hypoganglionosis) compared with the control group. Patients with megacolon were characterized by a substantial decrease in both the number and the process length of interstitial cells of Cajal. The myenteric plexus exhibited either complete aganglionosis or severe hypoganglionosis.
The enteric nervous system and interstitial cells of Cajal are altered concomitantly in slow-transit constipation and megacolon and may play a crucial role in the pathophysiology of colorectal motility disorders.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interstitial cells of Cajal (ICC) play a central role in coordinating normal gastrointestinal (GI) motility. Depletion of ICC numbers and network integrity contributes to major functional GI motility disorders. However, the mechanisms relating ICC structure to GI function and dysfunction remains unclear, partly because there is a lack of large-scale ICC network imaging data across a spectrum of depletion levels to guide models. Experimental imaging of these large-scale networks remains challenging because of technical constraints, and hence we propose the generation of realistic virtual ICC networks in silico using the Single Normal Equation Simulation (SNESIM) algorithm. ICC network imaging data obtained from wild-type (normal) and 5-HT2B serotonin receptor knockout (depleted ICC) mice were used to inform the algorithm, and the virtual networks generated were assessed using ICC network structural metrics and biophysically-based computational modeling. When the virtual networks were compared to the original networks, there was less than 10% error for four out of five structural metrics and all four functional measures. The SNESIM algorithm was then modified to enable the generation of ICC networks across a spectrum of depletion levels, and as proof-of-concept, virtual networks were successfully generated with a range of structural and functional properties. The SNESIM and modified SNESIM algorithms therefore offer an alternative strategy for obtaining large-scale ICC network imaging data across a spectrum of depletion levels. These models can be applied to accurately inform the physiological consequences of ICC depletion.
    IEEE transactions on bio-medical engineering 03/2015; DOI:10.1109/TBME.2015.2412533 · 2.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This review provides an overview of our understanding of motility and slow wave propagation in the stomach. It begins by reviewing seminal studies conducted by Walter Cannon and Augustus Waller on in vivo motility and slow wave patterns. Then our current understanding of slow wave patterns in common laboratory animals and humans is presented. The implications of slow wave dysrhythmic patterns that have been recorded in animals and patients suffering from gastroparesis are discussed. Finally, current challenges in experimental methods and techniques, slow wave modulation and the use of mathematical models are discussed.This article is protected by copyright. All rights reserved.
    Acta Physiologica 10/2014; 213(2). DOI:10.1111/apha.12406 · 4.25 Impact Factor
  • New Advances in Gastrointestinal Motility Research, Edited by L. K. Cheng, 01/2013: chapter Spatiotemporal mapping techniques for quantifying gut motility: pages 219-241; Dordrecht: Springer Science+Buisiness Media.

Full-text (2 Sources)

Available from
Jun 5, 2014