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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Morphometric quantification of normal submucous plexus in the distal rectum of adult healthy volunteers

OBJECTIVE: Inadequate morphometric characterization of the normal adult submucous plexus has precluded the diagnosis of colonic dysganglionoses associated with constipation, such as intestinal neuronal dysplasia type B (IND B). The internal submucous plexus (Meissner plexus) was morphometrically quantified in adult healthy volunteers. DESIGN: Open, prospective morphometric study in balanced groups of female and male volunteers. PARTICIPANTS: Thirty-seven adult healthy male and female volunteers with normal bowel function and no history of gastrointestinal disease. METHODS: Four jumbo rectal biopsies (3-5 mm3) were taken 5 and 10 cm above the pectinate line. Two expert gastrointestinal pathologists assessed biopsy sections after specific nerve cell staining for lactic dehydrogenase, nitric oxide synthase and acetylcholinesterase, mainly for characteristics of ganglia and nerve cells in the submucous plexus. RESULTS: No healthy individual demonstrated over 20% of submucosal ganglia as giant ganglia or more than four giant ganglia per 30 sections (the morphometric criteria for IND B). Single submucosal nerve cells and ganglion numbers halved between 10 and 5 cm above the pectinate line, but there were no age or gender differences. The biological variability of nerve cell and ganglion density in the submucous plexus was large. CONCLUSIONS: Healthy adults show less than 20% of submucosal ganglia as giant ganglia and no more than four giant ganglia per 30 rectal biopsy sections. There is therefore no overlap with the histomorphological criteria of IND B. These data therefore support the specificity of the previously defined criteria for IND B in adults.     

Das neurogene Megakolon: Liegt immer ein Morbus Hirschsprung zugrunde?

The development of megacolon in adults is attributed to malformations of the enteric nervous system apart from mechanic, metabolic, endocrinologic, pharmacologic, neurologic, infectious or systemic causes. Hirschsprung’s disease is considered to represent the most acknowledged form of intestinal innervation disorders underlying the formation of megacolon. In order to evaluate this association, morphologic alterations of the enteric nervous system were examined in patients (age: 19 to 67 years) with megacolon. From the resected colonic segments conventional serial sections and whole-mount preparations were obtained and submitted to immunohistochemical procedures for Protein Gene Product 9.5 as a neuronal marker allowing the 2-dimensional assessment of the architecture of the intramural nervous plexus layers. Whereas complete aganglionosis was diagnosed in only 25% of the cases examined, thus resembling classic Hirschsprung’s disease, the remaining colonic segments showed other forms of intestinal neuronal malformations: 1. Hypoganglionosis of varying severity, 2. intestinal neuronal dysplasia characterised by submucosal giant ganglia and concomitant hypertrophy of nerve fibers, 3. heterotopic ganglia located ectopically within the longitudinal muscle layer as well as within the lamina propria mucosae. In contrast to conventional histologic sections, whole-mount preparations allowed a more subtle assessment of the morphologic alterations of intramural nervous plexus from the normal to the pathologic area and, therefore, a more precise diagnostic classification of intestinal innervation disorders. It could be shown that neurogenic megacolon in adults is not only caused by aganglionosis but also by non-aganglionic innervation disorders. The findings implicate that in adolescent and adult patients suffering from intestinal motility disorders and a concomitant development of megacolon hypoganglionic conditions and intestinal neuronal dysplasia have to be taken into consideration in regards to the diagnostic and therapeutic approach.     

Morphometrie der Ganglien und Nervenzellen des Plexus submucosus bei der intestinalen neuronalen Dysplasie des Erwachsenen

Intestinal neuronal dysplasia is a developmental abnormality of the plexus submucosus in the colon. In recent years this initially in children described dysganglionosis has also been found in adults with chronic constipation. The aim of this study was a morphometric characterization of intestinal neuronal dysplasia in the submucous plexus of adults. Biopsies of 10 adults with intestinal neuronal dysplasia were compared with biopsies of 10 healthy controls. Nerve cells and ganglia were stained selectively with a lactate dehydrogenase reaction. Morphometry was made with an optic electronic analysis system. The detection of 6 to 10 giant ganglia with more than 7 nerve cells in 15 biopsy sections proved to be the most characteristic diagnostic indicator of intestinal neuronal dysplasia. The number of giant ganglia in the submucous plexus was 20%. For a quantitative objectivation of intestinal neuronal dysplasia 15 biopsy sections with enough submucosa are necessary.     

Differential changes in intrinsic innervation and interstitial cells of Cajal in small bowel atresia in newborns

AIM: To investigate morphological changes of the enteric nervous system (ENS) and the interstitial cells of Cajal (ICCs) in small bowel atresia.METHODS: Resected small bowel specimens from affected patients (n = 7) were divided into three parts (proximal, atretic, distal). Standard histology and enzyme immunohistochemistry anti-S100, anti-protein gene product (PGP) 9.5, anti-neurofilament (NF), antic-kit-receptor (CD117) was carried out on conventional paraffin sections of the proximal and distal part. RESULTS: The neuronal and glial markers (PGP 9.5, NF, S-100) were expressed in hypertrophied ganglia and nerve fibres within the myenteric and submucosal plexuses. Furthermore, the submucous plexus contained typical giant ganglia. The innervation pattern of the proximal bowel resembled intestinal neuronal dysplasia. The density of myenteric ICCs was clearly reduced in the proximal bowel, whereas a moderate number of muscular ICCs were found. The anti-CD117 immunore- action revealed additional numerous mast cells. The distal bowel demonstrated normal morphology and density of the ENS, the ICCs and the mast cells.CONCLUSION: The proximal and distal bowel in small bowel atresia revealed clear changes in morphology and density of the ENS and ICCs.     

Origins of peptide and norepinephrine nerves in the mucosa of the guinea pig small intestine

Norepinephrine, acetylcholine, and certain peptides are contained in mucosal nerves and have potent effects on transepithelial water and electrolyte fluxes. It is difficult to ascribe roles for these nerves as their sources are unknown. The present studies were undertaken to determine the origins of nerve fibers that are found in the mucosa of the guinea pig small intestine and which contain one of the following substances: vasoactive intestinal peptide, substance P, somatostatin, neuropeptide Y, cholecystokinin, or norepinephrine. Nerve fiber origins were ascertained by making lesions to sever pathways through which the nerves could reach the mucosa. The lesioning operations were homotopic autotransplants of short (2 cm) segments of intestine; myectomies, in which a 5-10-mm length of intestine was stripped of longitudinal muscle and myenteric plexus; and extrinsic denervation, in which nerves reaching the intestine through the mesentery were severed. The results of these studies, considered along with previously published work, led to the upcoming conclusions. Nerve fibers in the mucosa showing immunoreactivity for vasoactive intestinal peptide, somatostatin, cholecystokinin, and neuropeptide Y arise from cell bodies in the overlying submucous plexus. Substance P fibers arise in part from the overlying submucous plexus and in part from the overlying myenteric plexus. Mucosal norepinephrine fibers arise from extrinsic sympathetic ganglia. Enkephalin, gastrin-releasing peptide, and 5-hydroxytryptamine, which are in some enteric nerves, are not found in submucous nerve cells and few, if any, fibers containing these substances supply the mucosa. Thus, the mucosa receives a dense nerve supply, much of which arises locally from submucous ganglia.     

Submucosal hypoganglionosis causing chronic idiopathic intestinal pseudo-obstruction.

A 39-year-old woman presented with recurrent symptoms suggestive of intestinal obstruction. She was put on total parenteral nutrition (TPN) and consequently developed sepsis and endocarditis. TPN was stopped and a venting enterostomy was performed. Biopsies of mucosa and submucosa were taken at surgery; immunohistochemistry for neuronal proteins, protein gene product 9.5 (PGP 9.5) and the glial S-100-protein was done. Many enlarged nerve fiber strands were found in the submucosa. Few small ganglia containing a small number of nerve cells could be observed, suggesting hypoganglionosis. This patient with chronic idiopathic intestinal pseudoobstruction of neurogenic type had a defect in the submucous plexus, whereas visceral neuropathies are usually characterized by defects of the myenteric plexus with normal submucous plexus.     

Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease.

Widespread alterations of the gut autonomic nervous system have been described in Crohn's disease. Immunohistochemistry shows that these alterations are associated with the expression of major histocompatibility (MHC) class II antigens (HLA-DR) on enteroglial cells in the ganglia of the submucous and myenteric plexuses and on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and extensions do not express MHC class II antigens. The class II expression is associated with the presence of UCHL1-positive T lymphocytes. MHC class II expression can also be found on endothelial cells and vascular smooth muscle cells but not on smooth muscle cells of the muscularis mucosae or propria. The intensity of MHC class II expression on the glial cells of the enteric nervous plexus and on endothelial cells correlates well with the intensity of class II expression on epithelial cells.     

Immunohistochemical study of the colonic muscle and innervation in idiopathic chronic constipation

PURPOSE: This study was designed to investigate neural and muscular features of the colonic wall in patients with severe idiopathic constipation. METHODS: By using quantitative immunohistochemistry, resected specimens from 14 patients with idiopathic chronic constipation and 17 nonobstructed cancer controls were studied. RESULTS: Routine histology revealed no significant histologic abnormality throughout the colon apart from four cases of melanosis coli. Ratio of the thickness of circular to longitudinal muscle was significantly lower in the left colon in constipated subjects. The myenteric plexus appeared morphologically normal in all subjects. S-100 protein, which stains neuronal supporting tissues, demonstrated an increase in the proportion of neural tissue in the myenteric plexus. There was an increased number of PGP-9.5 immunoreactive nerve fibers in the muscularis propria in constipated patients, and this was significantly higher in the ascending and descending colon. CONCLUSION: Intractably constipated patients have alterations in the neural composition of the colonic myenteric plexus and innervation of the circular muscle.Supported by a grant from Yonsei University Research Foundation, Seoul, Korea. Dr. Talbot is supported in part by the Imperial Cancer Research Fund.     

Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia

BACKGROUND: A homozygous mutation of the endothelin B receptor (EDNRB) gene in spotting lethal (sl/sl) rats leads to Hirschsprung's disease (HSCR) with long segmented aganglionosis. However, the effects on the development of the enteric nervous system (ENS) promoted by a heterozygous mutation of the EDNRB gene are not known. The present study aimed to describe and morphometrically assess the phenotypic abnormalities of the ENS in heterozygous (+/sl) EDNRB deficient rats in comparison with homozygous (sl/sl) EDNRB deficient and wild-type (+/+) rats. METHODS: The distal small intestine, caecum, and colon were obtained from sl/sl, +/sl, and +/+ rats. To demonstrate the three dimensional organisation of the ENS, the intestinal wall was microdissected into wholemounts and incubated against the pan-neuronal marker protein gene product 9.5. Assessment of the ENS included morphometric quantification of ganglionic size and density, the number of nerve cells per ganglia, and the diameter of nerve fibre strands within both the myenteric and submucous plexus. RESULTS: Sl/sl rats were characterised by complete aganglionosis resembling the same histopathological features observed in patients with HSCR. +/sl rats revealed more subtle abnormalities of the ENS: the submucous plexus was characterised by a significantly increased ganglionic size and density, and the presence of hypertrophied nerve fibre strands. Morphometric evaluation of the myenteric plexus did not show statistically significant differences between +/sl and +/+ rats. CONCLUSIONS: In contrast with sl/sl rats, +/sl rats display non-aganglionated malformations of the ENS. Interestingly, these innervational abnormalities resemble the histopathological criteria for intestinal neuronal dysplasia (IND). Although IND has been described in several intestinal motility disorders, the concept of a clearly defined clinical-histopathological entity is still controversially discussed. The present findings support the concept of IND based on clearly defined morphological criteria suggesting a genetic link, and thus may provide a model for human IND. Furthermore, the data underline the critical role of the "gene dose" for the phenotypic effects promoted by the EDNRB/EDN3 system and confirm that the development of the ENS is not an "all or none" phenomenon.     

慢传输型便秘乙状结肠VIP,SP免疫组化研究

目的探讨慢传输型便秘（ＳＴＣ）的神经病理学基础。方法应用半定量免疫细胞组织化学的方法，对１４例ＳＴＣ和１１例非梗阻性直肠腺癌患者的乙状结肠标本进行研究，主要观察肠壁内血管活性肠肽（ＶＩＰ）和Ｐ物质（ＳＰ）的变化。结果常规ＨＥ染色下，两组结肠肌间神经丛无明显改变；免疫组化见ＳＴＣ患者乙状结肠壁内ＶＩＰ含量减少（Ｐ＜０．０５）；ＳＰ含量明显降低（Ｐ＜０．００１）；而粘膜层内无明显变化。结论ＳＴＣ患者结肠壁存在明显的神经病理学变化，其结肠传输减慢可能与肠壁内ＶＩＰ和ＳＰ能神经元数量减少和／或功能障碍有关。     

Changes in adrenergic and peptidergic nerves in the submucous plexus of streptozocin-diabetic rat ileum.

The effect of streptozocin diabetes on the distribution of adrenergic and peptidergic nerves in the submucous plexus of rat ileum was investigated and compared with the changes in the myenteric plexus of the same region of ileum. There was an increase in the intensity of immunoreactivity in vasoactive intestinal polypeptide- and neuropeptide Y-like immunoreactive nerve fibers and neurons and a decrease in calcitonin gene-related peptide-like immunoreactivity but no change in substance P- and dopamine beta-hydroxylase-like immunoreactivity in the nerve fibers and neurons of the submucous plexus of both 8- and 16-wk streptozocin-diabetic rat ileum. However, in the myenteric plexus of the diabetic rat ileum, there was enlargement of varicosities and an increase followed by a slight decrease in the intensity of immunoreactivity of vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-like immunoreactive nerve fibers and neurons, increased substance P-like immunoreactivity in diabetes at 16 wk, and an initial decrease (at 8 wk) followed by a recovery of calcitonin gene-related peptide-like immunoreactivity at 16 wk, but no change in neuropeptide Y-like immunoreactivity. The markedly different changes in peptidergic and adrenergic nerves between the two enteric plexuses show that diabetic neuropathy induced by streptozocin is not selective and involves factors other than neurotransmitter types.     

突触素单克隆抗体免疫组化实验诊断肠神经发育不良症的价值

为探讨肠神经发育不良症（IND）的有效诊断方法，对45例术前诊断为先天性巨结肠（HD）的慢性肠梗阻患儿行巨结肠根治手术，并对其结肠痉挛段标本进行突触素单克隆抗体免疫组化实验。结果显示，16例结肠标本可见粘膜下神经丛过渡增生并有巨神经节（诊断为IND），与正常对照组比较，P＜0．01，其中14例有异位神经节（9例合并HD，下称HAIND），其病理切片中发现有异位的神经节细胞，且部分神经节细胞有变形，空泡化；10例IND（其中8例HAIND）可固有层和粘膜肌染色增强，与正常对照组比较，P＜0．01。认为突触素单克隆抗体免疫组化实验显示粘膜一神经丛过度增生，巨神经节可作为诊断IND的硬性指标；异位神经节，固有层和粘膜肌染色增强可作为诊断IND的辅助指标。在病理切片中应用突触素单克隆抗体免疫组化实验，可清晰显示肠壁神经丛的发育情况，是诊断IND的可靠方法。     

应激对大鼠结肠神经系统nNOS表达的影响

目的:探讨应激对大鼠结肠神经系统nNOS表达的影响. 方法:SD大鼠30只随机分为对照组,应激组和L-NAME 组,采用水浸-束缚应激(WRS)动物模型,用免疫组织化学ABC法检测nNOS在大鼠结肠黏膜下神经丛和肌间神经丛的表达,应用计算机图像分析系统对其表达进行定量分析．结果:与对照组比较,应激组黏膜下神经丛和肌间神经丛的nNOS阳性神经元的灰度值明显减少(P=0．02或P =0．005),阳性神经元细胞数的平均密度增加(P=0．04 或P=0．01),表达增强,且在黏膜上皮细胞、固有层淋巴细胞也有nNOS表达．L-NAME组黏膜下神经丛和肌间神经丛的nNOS阳性神经元的灰度值较应激组增加 (P=0．04),平均密度下降(P=0．04或P=0．03),表达减弱,而与对照组比较均无明显差异(P>0．05)．结论:应激可引起大鼠结肠神经系统nNOS表达增强, 提示一氧化氮(NO)在应激所致的结肠功能失调中可能起重要作用．     

Reaggregation of Rat Dissociated Myenteric Plexus in Extracellular Matrix Gels

The aim of this study was to investigate the growth behavior of freshly dissociated myenteric plexus in a three-dimensional extracellular matrix (ECM) environment with and without stimulation of glial cell line-derived neurotrophic factor (GDNF). Therefore, cell suspensions of the dissected myenteric plexus of newborn rats were cultured in freshly prepared gels of commercially available mixtures of collagen, laminin, and hepatoglycans as a first step towards mimicking the natural environment of the myenteric plexus. The cultures were kept either in chemically defined serum-free medium alone or supplemented with GDNF. Cultures on polylysine-coated glass cover slips served as controls. Dissociated myenteric plexus grown on polylysine formed dense clusters of neurons with radially outgrowing nerve fibers, while the neurons cultured in the gel reaggregated to much smaller clusters. These contained, depending on the culture conditions, 2–10 neurons. The morphology of the network that was seen in the gels after a few days in vitro resembled very closely the in situ situation of the submucous plexus and the myenteric plexus in hypoganglionic children. Electron microscope investigations showed a high degree of organization with fiber bundles and vesicle-containing varicosities and growth cones. Independent of the method of culturing, GDNF obviously influenced the growth behavior of the dissociated plexus. The size of the ganglia was larger, and the secondary network denser when GDNF was supplemented. Moreover, the enteric neurons in the gel cultures tended to be larger in size when treated with GDNF. Three-dimensional cultures of dissociated myenteric plexus in an ECM gel might be a valuable tool towards the understanding of the formation of the enteric nervous system during development, especially considering pathological conditions such as Hirschsprungs disease or other dysganglionic diseases.     

Neurochemical coding in the small intestine of patients with Crohn''s disease.

BACKGROUND: There have been conflicting results regarding the effect of Crohn's disease on the neurochemical composition of the enteric nervous system. AIMS: To examine the effect of Crohn's disease on the neurochemical composition of enteric nerve fibres and cell bodies using whole mount preparations of human ileum. METHODS: Whole wall ileum from seven normal subjects and nine patients with Crohn's disease was used to investigate the neurochemical composition of neurones and nerve fibres in the myenteric plexus, circular muscle, and serosa layer of ileum using immunohistochemical techniques. RESULTS: Increased tyrosine hydroxylase, 5-hydroxytryptamine, and neuropeptide Y immunoreactivity was exclusively seen in the myenteric plexus. There was increased neurofilament immunoreactivity in the myenteric plexus and nerve fibres of the circular muscle layer, and thick bundles of immunoreactive nerve fibres in the serosa layer. Increased vasoactive intestinal polypeptide, nitric oxide synthase, and pituitary adenylate cyclase activating peptide immunoreactivity was seen in the myenteric plexus and nerve fibres of the circular muscle layer, and aggregates of inflammatory cells in the serosa layer of the afflicted segment of Crohn's ileum. In addition, there was a chaotic display of nerve fibres containing some of the neuroactive substances with a high frequency of enlarged varicosities in the myenteric ganglia and/or nerve fibres of the circular muscle layer of Crohn's ileum. CONCLUSION: Results show quantitative as well as qualitative changes in the neurochemical composition of enteric nerve fibres and nerve cell bodies of Crohn's ileum. These changes and the presence of nitric oxide synthase and peptides immunoreactive inflammatory cells in the serosa layer suggest that nerve-immune interactions may have a significant role in the process of the inflammatory changes seen in Crohn's ileitis.     

Role of Nitric Oxide in the Colon of Patients With Slow-Transit Constipation

PURPOSE: The cause of dysmotility in patients with slow-transit constipation is unknown. Nitric oxide has recently been shown to be a neurotransmitter in the nonadrenergic, noncholinergic inhibitory nerves of the human gut. To clarify the physiologic significance of nitric oxide in the colon of patients with slow-transit constipation, we investigated the enteric nerve responses in lesional and normal bowel segments derived from patients with slow-transit constipation and patients who underwent colon resection for colonic cancers. METHODS: Twenty-six preparations were taken from colonic lesions in eight patients with slow-transit constipation (2 men; age, 23 to 69 (mean, 44.8) years). Forty-two preparations were taken from the normal colons of 14 patients with colonic cancer (8 men; age, 40 to 66 (mean, 52.4) years). A mechanographic technique was used to evaluate in vitro muscle responses to electric field stimulation before and after treatment with various autonomic nerve blockers, NG-nitro-L-arginine, and L-arginine. RESULTS: The colons of patients with slow-transit constipation were more strongly innervated by nonadrenergic, noncholinergic inhibitory nerves than were normal colons (P <0.05). Nitric oxide was found to act on both normal and slow-transit constipation colons. The colons of patients with slow-transit constipation were more strongly innervated by nitric oxide nerves than were normal colons (P < 0.01). Responses to electric field stimulation were the same in each case among the normal colons and were also the same in each case among the slow-transit constipation colons. CONCLUSION: These findings suggest that an increase of nitric oxide mediates nonadrenergic, noncholinergic inhibitory nerves and plays an important role in the dysmotility observed in the colons of patients with slow-transit constipation.     

Substance P-containing nerves in the human small intestine. Distribution, ultrastructure, and characterization of the immunoreactive peptide

Light and electron microscopic immunocytochemical techniques were used to examine the distribution and ultrastructure of substance P-immunoreactive nerves in human jejunum and distal ileum. The organization of human enteric substance P-containing nerves closely resembled that in other species. Dense arrays of varicose immunofluorescent fibers occurred in myenteric and submucous ganglia (which contained immunoreactive nerve cell bodies) and in the mucosa. There were fibers in both muscle layers, in the muscularis mucosae, and around blood vessels. Fibers in the myenteric plexus contributed to both ascending and descending pathways. Substance P-immunoreactive axon profiles contained small round and large round vesicles and were apposed to nerve cell bodies, and nonimmunoreactive and immunoreactive axon profiles. Synapselike contacts were occasionally observed on nerve cell bodies and processes. The substance P-like material was characterized by high pressure liquid chromatography and radioimmunoassay and found to be indistinguishable from the authentic undecapeptide. These results suggest that enteric nerves containing substance P may play similar roles in humans as in other species.     

Nitric oxide synthase and VIP distribution in enteric nervous system in idiopathic chronic constipation

Idiopathic chronic constipation has been correlated to neural abnormalities that consist of a reduced number of myenteric plexus neurons and a decreased concentration of VIP-positive nerve fibers within the circular muscle. Recent studies hypothesized the involvement of nitric oxide in motility disorders of the human gut. To date, no information is available on nitric oxide involvement in idiopathic chronic constipation. The density of VIP- and nitric oxide-producing neurons was evaluated by immunocytochemistry using anti-VIP and anti-nitric oxide synthase antibodies in five patients with idiopathic chronic constipation. A low total neuron density was found at the myenteric plexus. The density of VIP-positive neurons was low while that of nitric oxide synthase-positive neurons was high at both plexuses. Our data confirm that idiopathic slow-transit chronic constipation is due to abnormal neurogenic factors. The presence of numerous nitric oxide synthase-positive neurons, all along the colon and at both plexuses, supports the hypothesis that an excessive production of nitric oxide may cause the persistent inhibition of contractions.Supported by MURST University Funds.     

慢传输型便秘发病机制的研究

慢传输型便秘(STC)的发病机制主要与肠神经系统(ENS)、Cajal间质细胞(ICC)、平滑肌、神经递质等有关。研究发现STC结肠组织中ENS出现退行性变化,肌间神经丛空泡变性,ICC数量减少,形态改变,平滑肌退行性变,多种神经递质发生改变。本文就STC发病机制的研究作一综述。