Immunohistochemical analysis of myenteric ganglia and interstitial cells of Cajal in ulcerative colitis

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease with alterations of colonic motility, which influence clinical symptoms. Although morpho-functional abnormalities in the enteric nervous system have been suggested, in UC patients scarce attention has been paid to possible changes in the cells that control colonic motility, including myenteric neurons, glial cells and interstitial cells of Cajal (ICC). This study evaluated the neural-glial components of myenteric ganglia and ICC in the colonic neuromuscular compartment of UC patients by quantitative immunohistochemical analysis. Full-thickness archival samples of the left colon were collected from 10 patients with UC (5 males, 5 females; age range 45–62 years) who underwent elective bowel resection. The colonic neuromuscular compartment was evaluated immunohistochemically in paraffin cross-sections. The distribution and number of neurons, glial cells and ICC were assessed by anti-HuC/D, -S100β and -c-Kit antibodies, respectively. Data were compared with findings on archival samples of normal left colon from 10 sex- and age-matched control patients, who underwent surgery for uncomplicated colon cancer. Compared to controls, patients with UC showed: (i) reduced density of myenteric HuC/D+ neurons and S100β+ glial cells, with a loss over 61% and 38%, respectively, and increased glial cell/neuron ratio; (ii) ICC decrease in the whole neuromuscular compartment. The quantitative variations of myenteric neuro-glial cells and ICC indicate considerable alterations of the colonic neuromuscular compartment in the setting of mucosal inflammation associated with UC, and provide a morphological basis for better understanding the motor abnormalities often observed in UC patients.

Long-term evolution and predictive factors of mild inflammatory bowel disease

“…This accumulation is suspected to progressively impair the intestinal function and the quality of life. [8] Active chronic UC can also induce a loss of colonic function [2] and an increased risk of colonic cancer. [9] Our definition of mild CD and UC also excluded the requirement of IM or anti-TNF in the course of the disease because they are usually associated with a worsening of the disease and with an increased incidence of infectious [10][11][12] and oncologic complications.…”

“…[1,2] The aim of CD and UC treatments is not only to induce a corticosteroid-free remission, but also to achieve mucosal healing to change the evolution of the disease. Immunomodulators (IMs) and particularly anti-TNFs are effective to induce mucosal healing in inflammatory bowel diseases (IBD).…”

Effects of Exogenous Interleukin-9 on the Growth, Proliferation and Activity of Interstitial Cells of Cajal Cultured in vitro

“…Recently, it was found that the damage, loss or function change of ICCs is closely associated with many GI motility disorders after inflammation [5][6][7] . Hence, further studies about the growth, development and maintaining mechanism of the network structure of ICCs in pathologic condition and the cytokines, which regulate the maintenance and survival of ICCs are of great clinical significance [8].…”

Effects of Inflammation on the Innervation of the Colon

“…A common finding from studies of the inflamed colon is a reduction in the number of enteric neurons that does not appear to be restricted to specific neural populations. This has been observed in the myenteric plexus of mouse and guinea pig (Boyer et al 2005;Linden et al 2005) and the submucosal plexus of rats (Sanovic et al 1999) with trinitrobenzene sulfonic acid (TNBS)-induced colitis, as well as the myenteric plexus of the human ulcerative colitis (UC) patients (Bernardini et al 2012;Geboes and Collins 1998). Enteric neuron density remains diminished following the resolution of inflammation (Linden et al 2005).…”