Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses.

Background: Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be either acute or chronic and is associated with adverse postnatal outcomes of the intestine, including necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells. Yet, the impact of acute, chronic, or repetitive antenatal inflammatory stimuli on the development of the intestinal mucosa and ENS has not been studied. The aim of this study was therefore to investigate the effect of acute, chronic, and repetitive microbial exposure on the intestinal mucosa, submucosa and ENS in premature lambs. Materials and Methods: A sheep model of pregnancy was used in which the ileal mucosa, submucosa, and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute), Ureaplasma parvum (UP) for 42 days (chronic), or repetitive microbial exposure (42 days UP with 2 or 7 days LPS). Results: IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and inflammation in the mucosal and submucosal layers of the gut. Repetitive microbial exposure did not further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural ENS alterations characterized by loss of PGP9.5 and S100ß immunoreactivity, whereas these changes were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days. Conclusion: The in utero loss of PGP9.5 and S100ß immunoreactivity following chronic UP exposure corresponds with intestinal changes in neonates with NEC and may therefore form a novel mechanistic explanation for the association of chorioamnionitis and NEC.

Mucosectomy disrupting the enteric nervous system causes contraction and shrinkage of gastrointestinal flaps: potential implications for augmentation cystoplasty.

INTRODUCTION: Augmenting the bladder with a seromuscular gastrointestinal flap is a promising alternative approach aiming for a mucus-free bladder augmentation; however, the contraction (shrinkage) of the flaps remains a major concern. Enteric nervous system (ENS) abnormalities cause a failure of relaxation of the intestinal muscle layers in motility disorders such as Hirschsprung's disease and intestinal neuronal dysplasia. In mammals, the submucosal enteric nervous plexus contains nitrergic inhibitory motor neurons responsible for muscle relaxation. The authors hypothesize that mucosectomy disconnects the submucosal nervous plexus from the myenteric plexus resulting in flap shrinkage. STUDY DESIGN: After ethical approval, mucosectomy was performed on vascularized flaps from the ileum, colon, and stomach in five anesthetized pigs. In Group (I), only the mucosa was scraped off with forceps, creating a sero-musculo-submucosal flap, while in Group (II), the mucosa and submucosa were peeled off as one layer, leaving a seromuscular flap. Isolated and detubularized segments served as control. The width of each flap was measured before and after the mucosectomy. The ENS was assessed by neurofilament immunohistochemistry in conventional sections and by acetylcholinesterase and NADPH-diaphorase enzyme histochemistry in whole-mount preparations. RESULTS: The stomach contracted to a lesser extent of its original width, 92.82 ± 7.86% in Group (I) and 82.24 ± 6.96% in Group (II). The ileum contracted to 81.68 ± 4.25% in Group (I) and to 72.675 ± 5.36% in Group (II). The shrinkage was most noticeable in the colon: 83.89 ± 15.73% in Group (I) and to 57.13 ± 11.51% in Group (II). One-way equal variance test showed significant difference (P < 0,05) between Group (I) and (II), comparing stomach with ileum and ileum with colon. The histochemistry revealed that the submucosal nervous plexus containing nitrergic inhibitory neurons was disconnected from the myenteric plexus in Group (II) of all specimens. CONCLUSION: Mucosectomy resulted in significant immediate shrinkage of the flaps. This was more expressed when also the submucosa was peeled off, thus fully disrupting the ENS. The shrinkage affected the stomach the least and the colon the greatest. This phenomenon should be taken into consideration when planning mucus-free bladder augmentation.

The Influence of Inflammation and Nerve Damage on the Neurochemical Characterization of Calcitonin Gene-Related Peptide-Like Immunoreactive (CGRP-LI) Neurons in the Enteric Nervous System of the Porcine Descending Colon.

The enteric nervous system (ENS), localized in the wall of the gastrointestinal tract, regulates the functions of the intestine using a wide range of neuronally-active substances. One of them is the calcitonin gene-related peptide (CGRP), whose participation in pathological states in the large intestine remains unclear. Therefore, the aim of this study was to investigate the influence of inflammation and nerve damage using a double immunofluorescence technique to neurochemically characterize CGRP-positive enteric nervous structures in the porcine descending colon. Both pathological factors caused an increase in the percentage of CGRP-positive enteric neurons, and these changes were the most visible in the myenteric plexus after nerve damage. Moreover, both pathological states change the degree of co-localization of CGRP with other neurochemical factors, including substance P, the neuronal isoform of nitric oxide synthase, galanin, cocaine- and amphetamine-regulated transcript peptide and vesicular acetylcholine transporter. The character and severity of these changes depended on the pathological factor and the type of enteric plexus. The obtained results show that CGRP-positive enteric neurons are varied in terms of neurochemical characterization and take part in adaptive processes in the descending colon during inflammation and after nerve damage.

Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy.

INTRODUCTION: Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. METHODS: Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. RESULTS: There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups. CONCLUSIONS: Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis.

Neurologic complications of bariatric surgery: involvement of central, peripheral, and enteric nervous systems.

Approximately one in three Americans is obese. Current society guidelines recommend bariatric surgery after conservative measures at weight loss have failed. The frequency of bariatric surgeries has increased significantly over the past decade. While considered both safe and effective, bariatric surgery presents a distinct set of risks. This review focuses on the neurological complications of bariatric surgery. Injuries have been reported at all levels of the nervous system, including the central, peripheral, and enteric nervous system. Injury can be classified according to time of presentation and location. The two main mechanisms of nerve injury are from mechanical injury or as a consequence of malnutrition. Encephalopathy, peripheral neuropathies, myelopathies, and radiculoneuropathies have all been reported. Mechanical injuries likely occur from mechanical compression. Malnutrition injuries result from multi-micronutrient deficiencies. The most likely candidates are vitamin B12, folate, zinc, thiamin, copper, vitamin A, and vitamin E deficiencies.

Dupliaciones entéricas en pacientes pediátricos / Enteric duplications in pediatric patients

Determinar la incidencia de duplicaciones del Tubo Digestivo en niños, en un período de 10 años. Estudio descriptivo, transversal, retrospectivo. Revisión de historias clínicas y biopsias en el Hospital de Niños JM de Los Ríos, desde 1998 a 2008. Variables: edad, sexo, presentación clínica, órgano duplicado, estudio diagnóstico y tratamiento. Se reportarón 11 pacientes con quistes de duplicación, 28% eran recién nacidos, 73% del sexo femenino. Predominó el dolor abdominal como síntoma de presentación en 28%. Se realizó diagnóstico prenatal en 18%. El órgano duplicado predominante fue intestino delgado 55%. Se realizó ecografía abdominal a 7 pacientes y de éstos en un 71% se diagnosticó duplicación intestinal antes de la cirugía. Se realizó exploración a cielo abierto en todos los casos y en 82% se realizó resección total del quiste. Las duplicaciones del tubo digestivo son poco frecuentes. El diagnóstico prenatal permite corregir el defecto en edades tempranas y disminuir su morbilidad. La ecografía es un método útil para el diagnóstico. La resección total de la duplicación es el tratamiento ideal...

Determining the incidence of duplications of digestive tube in children, during a 10-year term. Retrospective cross-sectioned descriptive study. Review of clinical records and biopsies in Hospital de Niños JM de Los Ríos, between 1998 and 2008. Variables: age, sex, clinical presentation, duplicated organ, study, diagnosis, and treatment. 11 patients were reported with duplication cysts: 28% was just-born, 73% was female. Abdominal pain prevailed as the presentation symptom in 28% of cases. Prenatal diagnosis was performed in 18% of cases. Small intestine was the prevailing duplicated organ: 55% of cases. Abdominal echography was performed in 7 patients, and out of which 71% was diagnosed with intestine duplication before surgery. Open sky exploration was carried out in all cases and total resection of cyst was performed in 82% of all cases. Duplications of the digestive tube uncommon. Prenatal diagnosis allows for correcting such defect in early age, thus reducing morbidity. Echography is a diagnosis helpful method. The ideal treatment for duplication is total resection...

A 5-HT(4)-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult.

BACKGROUND: It was recently reported that some 5-HT(4)-receptor agonists increased neuronal numbers and length of neurites in enteric neurons developing in vitro from immunoselected neural crest-derived precursors. We aimed to explore a novel approach in vivo to reconstruct the enteric neural circuitry that mediates a fundamental distal gut reflex. METHODS: The neural circuit insult was performed in guinea pigs by rectal transection and subsequent end-to-end one layer anastomosis. A 5-HT(4)-receptor agonist, mosapride citrate (10-100 micromol L(-1)) (applied for a patent) was applied locally at the anastomotic site. KEY RESULTS: Mosapride promoted the regeneration of the neural circuit in the impaired myenteric plexus and the recovery of the defecation reflex in the distal gut. Furthermore, mosapride generated neurofilament (NF)-, 5-HT(4)-receptor- and 5-bromo-2'-deoxyuridine (BrdU)-positive cells and surprisingly formed neural network in the newly formed granulation tissue at the anastomotic site 2 weeks after enteric nerve circuit insult. Possible neural stem cell markers, anti-distal less homeobox 2 (DLX2)- and p75-positive and NF-positive cells increased during the same time period. All actions by mosapride were inhibited by the specific 5-HT(4)-receptor antagonist, GR113808 (10 micromol L(-1)). CONCLUSIONS & INFERENCES: These results indicate that activation of enteric neural 5-HT(4)-receptors promotes reconstruction of an enteric neural circuit leading to the recovery of the defecation reflex in the distal gut, and that this reconstruction involves possibly neural stem cells. These findings indicate that treatment with 5-HT(4) agonists could be a novel therapy for generating new enteric neurons to rescue aganglionic gut disorders.