Academic literature on the topic 'Colon myenteric plexus'

At present, there are no generally acceptable criteria for the evaluation of hypoganglionosis of the myenteric plexus. The aim of this morphometrical investigation was to examine the most important quantitative characteristics of hypoganglionosis. Colon specimens from 35 children with Hirschsprung's disease were assessed morphometrically. Twenty specimens with Hirschsprung's disease and proximal hypoganglionosis of the myenteric plexus were compared with 15 specimens with Hirschsprung's disease and normal innervation in the proximal myenteric plexus. All native surgical specimens were caudocranial coiled and sectioned in a cryostat. Nerve cells and ganglia were selectively stained with an enzyme-histochemical lactic dehydrogenase reaction. Morphometric measurements were done with an optic-electronic image analysis system. Hirschsprung's disease–associated hypoganglionosis of the myenteric plexus is characterized by a significant decrease in ganglion cross-sectional area (-56.2%) and in plexus area per mm colon (-53.5%). Together with these data, an increase in ganglion distance (+20%) was also determined, and the number of nerve cells per mm colon was decreased by −25.5%. The decrease in ganglion area and in the number of nerve cells per mm colon in the myenteric plexus proved to be the most characteristic parameters of a hypoganglionosis.

The interstitial cells of Cajal (ICC) are thought to play an important role in the control of gut motility. The regional and transmural pattern of distribution of ICC in the normal human colon and rectum was evaluated with immunohistochemistry using an anti-c- kit antibody. The transmural distribution of ICC was constant throughout the whole colon, the density of ICC was significantly greater at the myenteric plexus than at either the longitudinal or circular muscle layers, and in the rectum the transmural distribution was more even. Regionally, at the myenteric plexus, the transverse colon had a significantly greater density of ICC compared with the right colon ( P = 0.038), left colon ( P = 0.006), and rectum ( P = 0.008). The pattern of distribution of ICC identified in this study is consistent with the proposed roles of ICC as colorectal pacemakers, intermediaries of the neural control of muscle activity, and coordinators of colorectal muscle activity. The highest density of ICC was at the myenteric plexus of the transverse colon, which is the proposed region of pacemaking activity.

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon.

We have carried out a detailed ultrastructural study of the interstitial cells near the myenteric plexus of the canine colon and defined the structural characteristics which distinguish them from other resident non-neural cells. We have also examined the interconnections of these interstitial cells with nerves, the longitudinal muscle, and the circular muscle. In addition, we sought connections between interstitial cells of the myenteric plexus and those described earlier at the inner border of the circular muscle in proximal and distal colon. The interstitial cells of the myenteric plexus were structurally distinctive, and made gap junctions with one another and occasionally with smooth muscle. There seemed to be two subsets of these interstitial cells, one associated with the longitudinal muscle and the other with the circular muscle. Cells of both subsets were often close (≤20 nm) to nerve profiles. The interstitial cells near the longitudinal muscle layer penetrated slightly into the muscle layer, but those near the circular muscle did not and neither set contacted the other. Moveover, interstitial cells of Cajal located near the myenteric plexus were never observed to contact those at the inner border of circular muscle. The interstitial cells of Cajal at the canine colon myenteric plexus are structurally organized to provide independent pacemaking activities for the longitudinal and adjacent circular muscle. Their dense innervation suggests that they mediate neural modulation of intestinal pacemaker activities. Moreover, they lack direct contacts with the interstitial cell network at the inner border of circular muscle, which is essential for the primary pacemaking activity of circular muscle. The structural organization of interstitial cells in canine colon is consistent with their proposed role in pacemaking activity of the two muscle layers.Key words: pacemakers, neuromodulation, interstitial cells of Cajal.

Background Inflammatory bowel diseases are associated with remodeling of neuronal circuitries within the enteric nervous system, occurring also at sites distant from the acute site of inflammation and underlying disturbed intestinal functions. Homeoproteins orthodenticle OTX1 and OTX2 are neuronal transcription factors participating to adaptation during inflammation and underlying tumor growth both in the central nervous system and in the periphery. In this study, we evaluated OTX1 and OTX2 expression in the rat small intestine and distal colon myenteric plexus after intrarectal dinitro-benzene sulfonic (DNBS) acid-induced colitis. Methods OTX1 and OTX2 distribution was immunohistochemically investigated in longitudinal muscle myenteric plexus (LMMP)-whole mount preparations. mRNAs and protein levels of both OTX1 and OTX2 were evaluated by qRT-PCR and Western blotting in LMMPs. Results DNBS-treatment induced major gross morphology and histological alterations in the distal colon, while the number of myenteric neurons was significantly reduced both in the small intestine and colon. mRNA levels of the inflammatory markers, TNFα, pro-IL1β, IL6, HIF1α and VEGFα and myeloperoxidase activity raised in both regions. In both small intestine and colon, an anti-OTX1 antibody labeled a small percentage of myenteric neurons, and prevalently enteric glial cells, as evidenced by co-staining with the glial marker S100β. OTX2 immunoreactivity was present only in myenteric neurons and was highly co-localized with neuronal nitric oxide synthase. Both in the small intestine and distal colon, the number of OTX1- and OTX2-immunoreactive myenteric neurons significantly increased after DNBS treatment. In these conditions, OTX1 immunostaining was highly superimposable with inducible nitric oxide synthase in both regions. OTX1 and OTX2 mRNA and protein levels significantly enhanced in LMMP preparations of both regions after DNBS treatment. Conclusions These data suggest that colitis up-regulates OTX1 and OTX2 in myenteric plexus both on site and distantly from the injury, potentially participating to inflammatory-related myenteric ganglia remodeling processes involving nitrergic transmission.

BACKGROUNDNitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung’s disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group.AIMSTo determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood.METHODSSpecimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated.RESULTSThe myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus.CONCLUSIONSThe notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.

Abstract Background IBD frequently causes chronic abdominal pain and visceral hypersensitivity. To understand development of pain in IBD in more detail, we analyzed the inflammatory infiltration of the enteric nervous system (ENS). A crucial signaling point for pain transmission is the myenteric plexus situated in the smooth muscle layer of the colon wall. We investigated (i) the immune cell infiltration within the myenteric plexus, (ii) neuronal cell survival and (iii) expression of neurotransmitters by immunostaining in surgical colonic samples from patients with Crohn′s disease (CD) or ulcerative colitis (UC). Methods FFPE material from surgeries (ileocecal resections and colectomies) was collected from 12 UC, nine CD and 11 patients that received surgeries for non-inflammatory reasons (controls). Immune cell composition, neurotransmitter expression and cell survival were analyzed by quantifying immune cell infiltration of the myenteric ganglia in immunohistochemistry sections. Immune cells within the myenteric plexus were defined as intraganglionar cells. The neurotransmitters CGRP and substance P as well as annexin V as a cell death marker were quantified based on their expression within the myenteric ganglia. Results CD3+CD4+ intraganglionar T-cells (216 ± 44 cells/mm²) were found to be increased for CD myenteric plexus compared to controls (79 ± 35 cells/mm²) (p=0.04) (see Fig. 1). For CD and UC, the cell counts of CD3+CD8+ lymphocytes infiltrating the myenteric plexus were significantly increased (controls: 39 ± 18 cells/mm², CD: 281 ± 105 cells/mm² (p=0.0004), UC: 177 ± 59 cells/mm² (p=0.04), Intraganglionar Foxp3+ T-cells were not significantly changed. Intraganglionar CD163+ and CD68+ monocytes were increased in CD (CD68+ monocytes: control: 377 ± 50 cells/mm², CD: 1278 ± 264 cells/mm², p=0.002 and CD163+ monocytes: control: 501 ± 97 cells/mm², CD: 963 ± 236 cells/mm², p=0.04). Expression levels of the neurotransmitter CGRP were found to be increased for UC myenteric plexus (control: 1.8 ± 0.2 units of intensity, UC: 2.8 ± 0.2 units of intensity, p=0.005). Substance P was found to be reduced in the myenteric plexus of CD patients if compared to controls (control: 2.1 ± 0.1 units of intensity, CD: 1.5 ± 0.2 units of intensity, p=0.007). UC myenteric plexus showed more annexin V-positive cells than control patients. Conclusion The intraganglionar immune cell composition of myenteric plexus in IBD comprises CD3+CD4+, CD3+CD8 T-cells in UC and CD3+CD4+, CD3+CD8+ and CD3+Foxp3+ T-cells as well as CD68+ and CD163+ monocytes in CD. In UC myenteric ganglia levels of the neurotransmitter CGRP are increased whereas substance P expression is reduced in CD. UC-affected myenteric plexus show increased levels of apoptosis in comparison to controls.

Oxaliplatin (platinum-based chemotherapeutic agent) is a first-line treatment of colorectal malignancies; its use associates with peripheral neuropathies and gastrointestinal side effects. These gastrointestinal dysfunctions might be due to toxic effects of oxaliplatin on the intestinal innervation and glia. Male Balb/c mice received intraperitoneal injections of sterile water or oxaliplatin (3 mg/kg/d) triweekly for 2 weeks. Colon tissues were collected for immunohistochemical assessment at day 14. The density of sensory, adrenergic, and cholinergic nerve fibers labeled with calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH), and vesicular acetylcholine transporter (VAChT), respectively, was assessed within the myenteric plexus of the distal colon. The number and proportion of excitatory neurons immunoreactive (IR) against choline acetyltransferase (ChAT) were counted, and the density of glial subpopulations was determined by using antibodies specific for glial fibrillary acidic protein (GFAP) and s100β protein. Oxaliplatin treatment induced significant reduction of sensory and adrenergic innervations, as well as the total number and proportion of ChAT-IR neurons, and GFAP-IR glia, but increased s100β expression within the myenteric plexus of the distal colon. Treatment with oxaliplatin significantly alters nerve fibers and glial cells in the colonic myenteric plexus, which could contribute to long-term gastrointestinal side effects following chemotherapeutic treatment.

The etiology of denervation hypersensitivity was studied using a rat model. Degeneration of the myenteric plexus was produced by direct application of 0.1% benzalkonium chloride to the serosal surface of the distal colon. Thirty days later, the treated group was compared with a control group undergoing a sham operation. The treated group showed that the decreased number of ganglion cells of the myenteric plexus on routine stain and acetylcholinesterase staining demonstrated the myenteric plexus in the treated group diminished acetylcholinesterase activity. Methacholine (1%), a muscarinic agonist, increased intraluminal pressure in treated but not control rats. The dose-response curve of colonic muscle strips to oxotremorine showed a shift to the left, indicating greater sensitivity, in the treated bowel, with a 50% effective dose (ED50) of 2.5 x 10(-8) in treated muscle and 2.2 x 10(-7) in controls. Binding studies using [3H]quinuclidinyl benzilate ([3H]QNB) showed that the specific maximal binding (Bmax) for [3H]QNB was greater in treated than in untreated animals (228 +/- 26.1 and 135 +/- 42.9 fmol/mg protein, respectively; P < 0.01), even though the dissociation constants (Kd) were the same (0.398 +/- 0.083 and 0.406 +/- 0.065). These findings show that acquired denervation hypersensitivity in this model is due to an increase in the number of muscarinic acetylcholine receptors.

Este projeto, analisou a distribuição dos neurônios nos plexos mioentérico (PM) e submucoso (PS) imunorreativos aos receptores P2X2 (ir) e P2X7 (ir), calbindina (Calb-ir), calretinina (Calr-ir), colina acetil transferase (ChAT-ir) e ao óxido nítrico sintase (NOS-ir) do colo distal de ratos submetidos à desnutrição a renutrição protéica. Utilizaram-se colos distais de ratos nutridos (N42), desnutridos (D42) e renutridos (RN42). Os resultados do plexo PM, demonstraram que 100% dos neurônios Calb-ir, Calr-ir, ChAT-ir e NOS-ir, expressavam os receptores P2X2-ir e P2X7-ir nos três grupos. A densidade neuronal no PM, demonstrou um aumento de 20% a 97% dos neurônios receptores P2X2-7-ir, Calr-ir, ChAT-ir e NOS-ir e no PS foi de 29% a 75%, ambos D42 e recuperação no RN42. O perfil neuronal P2X7-ir, Calb-ir, Calr-ir e ChAT-ir do PM demonstrou diminuição de 28% a 40% e no PS os neurônios P2X2-7-ir, Calb-ir e ChAT-ir de 19% a 47% no D42. Concluí-se que, a desnutrição afeta os neurônios entéricos havendo recuperação na renutrição, podendo influenciar nas funções gastrintestinais.
The aim of the work was to analyze the distal colon myenteric (MN) and submucous (SN) neurons immunoreactive for P2X2-7 receptors, calbindin (Calb-ir), calretinin (Calr-ir), choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) of the animals submitted to undernutrition and refeeding proteic. Distal colon was used from nourished (N42), undernourished (D42) and refeeding (RN42) rats. The results have shown 100% coexpression of the myenteric and submucous Calb-ir, Calr-ir, ChAt-ir e NOS-ir neurons with P2X2-7-ir receptors. The MN density have shown increase of the 20% and 97% of the P2X2-7-ir, Calr-ir, ChAT-ir e NOS-ir neurons of the D42 group, and the SN have been increased 29% a 75% in the D42 group. In the MN neuronal profile have shown decrease P2X7-ir, Calb-ir, Calr-ir and ChAT-ir neurons of the 28% to 40% and in the PS P2X2-7-ir, Calb-ir and ChAT-ir of the 19% a 47% neurons in the D42 group. I concluded that, the undernutrition affects the enteric neurons and there was recuperation in the refeeding, this can influence the gastrintestinal functions.

O objetivo desta pesquisa foi quantificar os neurônios mioentéricos do jejuno e do colo durante o desenvolvimento pós-natal de ratos Wistar utilizando morfometria com enfoque estereológico e analisar as mudanças na área ocupada por neurônios e axônios mediante Sistemas de Informação Geográfica (SIG). Foram usadas 20 fêmeas de ratos da linhagem Wistar, divididas em grupos de acordo com a idade pós-natal em dias (G0, G7, G21 e G60). A análise morfométrica foi realizada em preparados totais de membrana usando azul cuprolínico, histoquímica para acetilcolinesterase (AChE) e NADPH-diaforase (NADPH-d), e imuno-histoquímicas para VIP e substância P. Foram estimadas a densidade numérica neuronal/área de superfície serosa, o número total de neurônios por segmento e a área neuronal média. A análise da área ocupada por neurônios e axônios foi realizada a partir de imagens de NADPH-d e AChE. Ocorreu uma diminuição significativa na densidade neuronal/área, nos neurônios totais e nos neurônios nitrérgicos a partir de G7 no jejuno e de G0 no colo, e nos neurônios colinérgicos entre G0 e G7 no jejuno e G0 e G21 no colo. O número total de neurônios corados com azul cuprolínico aumentou significativamente no colo a partir de G7; houve aumento dos neurônios nitrérgicos entre G7 e G21 e nos neurônios colinérgicos entre G21 e G60. No jejuno somente houve aumento do número total de neurônios nitrérgicos entre G0 e G7. Também foi percebido um aumento significativo na área dos neurônios nitrérgicos a partir de G7 no jejuno e de G0 no colo, e dos neurônios colinérgicos entre G7 e G21 no jejuno e G0 e G21 no colo. A área ocupada pelos axônios aumentou entre os grupos G0 e G7, diminuiu entre G7 e G21 e aumentou de novo entre G21 e G60. Estes resultados demonstraram que os neurônios e os axônios sofrem mudanças morfológicas e químicas durante o desenvolvimento pós-natal do sistema nervoso entérico, provavelmente devido a fatores microambientais como os fatores de crescimento e de replicação, a alimentação e o próprio crescimento do intestino. É possível que a completa maturidade do intestino somente seja completada quando este finaliza o seu processo de crescimento.
The aim of this study was to quantify jejunum and colon myenteric neurons during postnatal development in Wistar rats using morphometry and to analyse the changes in the area occupied by neurons and axons using Geographic Information Sistem (GIS). Twenty female Wistar rats divided in groups according to the age in days (G0, G7, G21 e G60) were used. Whole mount preparations using cuprolinic blue (CB), histochemistry for acetyl-cholinesterase (AChE) and NADPH-diaphorase (NADPH-d) and immunohistochemistry for VIP and substance P were used for morphometric evaluation. Neuronal numerical density/area of serosal surface, total number of neurons for segment and mean neuronal area were estimated. Analyses of the area ocuppied by neurons and axons were performed using images of NADPH-d and AChE. This study showed a significant decrease in the neuronal numerical density/area in total and nitrergic neurons from G7 in jejunum and G0 in colon, and in cholinergic neurons from G0 and G7 in jejunum and G0 and G21 in colon. In colon, total number of neurons increased significantly in cuprolinic blue stain from G7, in NADPH-d between G7 and G21 and in AChE between G21 and G60. In jejunum, there was a significant increase in the same parameter between G0 and G7 in NADPH-d. There was also a significant increase in the mean area of nitrergic neurons from G7 in jejunum and from G0 in colon, and in cholinergic neurons between G7 and G21 in jejunum and between G0 and G21 in colon. The area occupied by axons increased between G0 and G7, between G7 and G21 decreased and increased again between G21 and G60. This results showed that neurons and axons suffer morphologic and chemical changes during postnatal development in the enteric nervous system, probably due to micro-environmental factors as growth and replication factors, nutrition and growing of the intestine. It is possible that complete maturity of the intestine is achieved when it finishes its growing process.

Cisplatin, carboplatin and oxaliplatin are platinum-based agents that are amongst the most widely used drugs for the treatment of cancer in the clinical setting. Despite their therapeutic efficacy, these platinum-based drugs are associated with a myriad of dose-limiting side-effects. These include acute and chronic peripheral neuropathies (paraesthesias, dysaesthesias), and gastrointestinal complications (nausea, vomiting, constipation and diarrhoea). These side-effects decrease quality of life and cause life-threatening cardiac and renal sequeale consequent to malnutrition, dehydration and fluid and electrolyte imbalances, which in severe cases, can lead to death. Extensive research into the mechanisms underlying chronic peripheral neuropathies associated with platinum-based agents has focused on drug accumulation within the dorsal root ganglia (DRG). Only recently, a few studies have demonstrated damage to the enteric nervous system (ENS) following platinum-based chemotherapy. The ENS is an intrinsic and complex orchestration of nerves embedded throughout the entirety of the gastrointestinal tract innervating the musculature and mucosa. The mechanisms underlying ENS toxicity remain unknown. Furthermore, the gastrointestinal tract receives extrinsic innervations and it is also unknown if these nerves are vulnerable to platinum-based drugs. Platinum-based drugs mediate their cytotoxic effects through the formation of interstrand and intrastrand DNA adducts, particularly binding to the N7 position of guanine nucleotides. Essentially, these platinum lesions inhibit DNA replication through the distortion of the helical structure. DNA damage typically results in the induction of canonical apoptotic cascades. Until recent years apoptosis was deemed an immunologically ‘silent’ or ‘tolerogenic’ event. However, unlike cisplatin and carboplatin, there is substantial evidence shown in models of cancer that oxaliplatin prompts a fatal immune response against cells committed to apoptosis. This phenomenon is termed ‘immunogenic cell death’. Oxaliplatin-induced cytotoxicity results in the hallmark presentation of damage-associated molecular patterns (DAMPs) which can be recognised by antigen-presenting cells, and thus, stimulating phagocytosis of apoptotic cells and/or debris. The gastrointestinal tract harbours ~70% of the body’s immune system, and so it is unknown whether oxaliplatin treatment can induce changes in immunological responses which may directly or inadvertently induce ENS damage. Given the bi-directional communication between the immune and nervous systems, exploring the consequences of oxaliplatin-induced cytotoxicity and potential immunogenicity may provide insight into the multifaceted mechanisms underlying neuronal damage and death which impact gastrointestinal function.