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Biomolecules Oct 2023No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical...
No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop-Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.
Topics: Infant, Newborn; Humans; Cohort Studies; Retrospective Studies; Intestines; Enterostomy; Surgical Stomas
PubMed: 37892242
DOI: 10.3390/biom13101560 -
Neurogastroenterology and Motility Jan 2024Accurately reporting the identity and representation of enteric nervous system (ENS) neuronal subtypes along the length of the gastrointestinal (GI) tract is critical to...
BACKGROUND
Accurately reporting the identity and representation of enteric nervous system (ENS) neuronal subtypes along the length of the gastrointestinal (GI) tract is critical to advancing our understanding of ENS control of GI function. Reports of varying proportions of subtype marker expression have employed different dissection techniques to achieve wholemount muscularis preparations of myenteric plexus. In this study, we asked whether differences in GI dissection methods could introduce variability into the quantification of marker expression.
METHODS
We compared three commonly used methods of ENS wholemount dissection: two flat-sheet preparations that differed in the order of microdissection and fixation and a third rod-mounted peeling technique. We also tested a reversed orientation variation of flat-sheet peeling, two step-by-step variations of the rod peeling technique, and whole-gut fixation as a tube. We assessed marker expression using immunohistochemistry, genetic reporter lines, confocal microscopy, and automated image analysis.
KEY RESULTS AND CONCLUSIONS
We found no significant differences between the two flat-sheet preparation methods in the expression of calretinin or neuronal nitric oxide synthase (nNOS) as a proportion of total neurons in ileum myenteric plexus. However, the rod-mounted peeling method resulted in decreased proportion of neurons labeled for both calretinin and nNOS. This method also resulted in decreased transgenic reporter fluorescent protein (tdTomato) for substance P in distal colon and choline acetyltransferase (ChAT) in both ileum and distal colon. These results suggest that labeling among some markers, both native protein and transgenic fluorescent reporters, is decreased by the rod-mounted mechanical method of peeling. The step-by-step variations of this method point to mechanical manipulation of the tissue as the likely cause of decreased labeling. Our study thereby demonstrates a critical variability in wholemount muscularis dissection methods.
Topics: Mice; Animals; Myenteric Plexus; Calbindin 2; Enteric Nervous System; Neurons; Colon
PubMed: 37882149
DOI: 10.1111/nmo.14693 -
European Journal of Pharmacology Dec 2023Gastric lesions have several aetiologies, among which stress is the most prominent. Therefore, identification of new therapies to prevent stress is of considerable...
Gastric lesions have several aetiologies, among which stress is the most prominent. Therefore, identification of new therapies to prevent stress is of considerable importance. Alpha-ketoglutarate (α-kg) several beneficial effects and has shown promise in combating oxidative stress, inflammation, and premature aging. Thus, this study aimed to evaluate the protective effect of α-kg in a gastric damage model by water-immersion restraint stress (WIRS). Pretreatment with α-kg decreased stress-related histopathological scores of tissue oedema, cell loss, and inflammatory infiltration. The α-kg restored the percentage of type III collagen fibres. Mucin levels were preserved as well as the structure and area of the myenteric plexus ganglia were preserved after pretreatment with α-kg. Myeloperoxidase (MPO) levels and the expression of pro-inflammatory cytokines (TNF-α and IL-1β) were also reduced following α-kg pretreatment. Decreased levels of glutathione (GSH) in the stress group were restored by α-kg. The omeprazole group was used as standard drug e also demonstrated improve on some parameters after the exposition to WIRS as inflammatory indexes, GSH and mucin. Through this, was possible to observe that α-kg can protect the gastric mucosa exposed to WIRS, preserve tissue architecture, reduce direct damage to the mucosa and inflammatory factors, stimulate the production of type III collagen and mucin, preserve the myenteric plexus ganglia, and maintain antioxidant potential. Due to, we indicate that α-kg has protective activity of the gastric mucosa, demonstrating its ability to prevent damage associated with gastric lesions caused by stress.
Topics: Mice; Animals; Ketoglutaric Acids; Stomach Ulcer; Collagen Type III; Immersion; Gastric Mucosa; Glutathione; Mucins; Water; Restraint, Physical
PubMed: 37871764
DOI: 10.1016/j.ejphar.2023.176118 -
Frontiers in Immunology 2023Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However,...
Macrophage regulation of the "second brain": CD163 intestinal macrophages interact with inhibitory interneurons to regulate colonic motility - evidence from the rat model.
Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on gastrointestinal motility through interaction with myenteric neurons that contribute to the gut-brain axis, but this mechanism is yet to be properly characterised. The CX3CR1 chemokine receptor is expressed in the majority of intestinal macrophages, so we used a conditional knockout (diphtheria toxin receptor) rat model to transiently ablate these cells. We then utilized video imaging to evaluate colonic motility. Our previous studies in brain suggested that -expressing cells repopulate by 7 days after depletion in this model, so we performed our experiments at both the 48 hr (macrophage depletion) and 7-day (macrophage repopulation) time points. We also investigated whether inhibitory neuronal input driven by nitric oxide from the enteric nervous system is required for the regulation of colonic motility by intestinal macrophages. Our results demonstrated that CD163-positive resident intestinal macrophages are important in regulating colonic motility in the absence of this major inhibitory neuronal input. In addition, we show that intestinal macrophages are indispensable in maintaining a healthy intestinal structure. Our study provides a novel understanding of the interplay between the enteric nervous system and intestinal macrophages in colonic motility. We highlight intestinal macrophages as a potential therapeutic target for gastrointestinal motility disorders when inhibitory neuronal input is suppressed.
Topics: Animals; Rats; Brain; Heparin-binding EGF-like Growth Factor; Interneurons; Macrophages
PubMed: 37868978
DOI: 10.3389/fimmu.2023.1269890 -
Current Medicinal Chemistry Oct 2023The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses:...
The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.
PubMed: 37855342
DOI: 10.2174/0109298673260479231010044020 -
Neurogastroenterology and Motility Dec 2023Our main goals were to investigate the effects of L-glutathione (1%) treatment in Walker-256 tumor-bearing rats by analyzing immunoreactive neurons (IR), responsive to...
AIMS
Our main goals were to investigate the effects of L-glutathione (1%) treatment in Walker-256 tumor-bearing rats by analyzing immunoreactive neurons (IR), responsive to the nNOS enzyme and 3-Nitrotyrosine, in their jejunum myenteric plexus. Moreover, the oxidative state and inflammatory process in these animals were investigated.
METHODS
Four experimental groups were utilized: control (C), control treated with L-glutathione (CGT), Walker-256 tumor-bearing rats (TW), and Walker-256 tumor-bearing rats treated with L-glutathione (TWGT). After 14 days of tumor inoculation, the jejunum was collected for immunohistochemical techniques and assessment of oxidative status. Plasma was collected to evaluate oxidative status and measure cytokines.
RESULTS
The TW group exhibited a decrease of reduced glutathione in their jejunum, which was prevented in the L-glutathione treated TWGT group. TW animals presented pronounced oxidative stress by increasing levels of lipoperoxidation in their jejunum and malondialdehyde in their plasma; however, the L-glutathione treatment in TWGT group was not able to avoid it. The total antioxidant capacity was altered in groups TW and TWGT, yet the last one had a better index in their plasma. The IL-10, and TNF-α levels increased in TWGT animals. The nNOS-IR neuron density decreased in the jejunum myenteric plexus of the TW group, which was avoided in the TWGT group. The nNOS +3-Nitrotyrosine neurons quantification did not show significative alterations.
CONCLUSION
The treatment with L-glutathione (1%) imposed an important defense to some parameters of oxidative stress induced by TW-256, leading to neuroprotection to the loss in the nNOS-IR neuron density.
Topics: Rats; Animals; Jejunum; Nitrergic Neurons; Rats, Wistar; Neuroprotection; Oxidative Stress; Glutathione; Myenteric Plexus; Neoplasms
PubMed: 37831748
DOI: 10.1111/nmo.14688 -
Developmental Biology Jan 2024BAZ1B is one of 25-27 coding genes deleted in canonical Williams syndrome, a multi-system disorder causing slow growth, vascular stenosis, and gastrointestinal...
BAZ1B is one of 25-27 coding genes deleted in canonical Williams syndrome, a multi-system disorder causing slow growth, vascular stenosis, and gastrointestinal complaints, including constipation. BAZ1B is involved in (among other processes) chromatin organization, DNA damage repair, and mitosis, suggesting reduced BAZ1B may contribute to Williams syndrome symptoms. In mice, loss of Baz1b causes early neonatal death. 89.6% of Baz1b mice die within 24 h of birth without vascular anomalies or congenital heart disease (except for patent ductus arteriosus). Some (<50%) Baz1b were noted to have prolonged neonatal cyanosis, patent ductus arteriosus, or reduced lung aeration, and none developed a milk spot. Meanwhile, 35.5% of Baz1b mice die over the first three weeks after birth. Surviving Baz1b heterozygotes grow slowly (with variable severity). 66.7% of Baz1b mice develop bowel dilation, compared to 37.8% of wild-type mice, but small bowel and colon transit studies were normal. Additionally, enteric neuron density appeared normal in Baz1b mice except in distal colon myenteric plexus, where neuron density was modestly elevated. Combined with several rare phenotypes (agnathia, microphthalmia, bowel dilation) recovered, our work confirms the importance of BAZ1B in survival and growth and suggests that reduced copy number of BAZ1B may contribute to the variability in Williams syndrome phenotypes.
Topics: Animals; Mice; Colon; DNA Repair; Ductus Arteriosus, Patent; Neurons; Williams Syndrome
PubMed: 37827362
DOI: 10.1016/j.ydbio.2023.09.007 -
Science China. Life Sciences Feb 2024Weaning piglets usually suffer from severe diarrhea (commonly known as postweaning diarrhea, PWD) along with intestinal motility disorder. Intestinal peristalsis is...
Weaning piglets usually suffer from severe diarrhea (commonly known as postweaning diarrhea, PWD) along with intestinal motility disorder. Intestinal peristalsis is mainly regulated by the longitudinal muscle-myenteric plexus (LM-MP). To understand the relationship between intestinal LM-MP function and the development of PWD, we compared the intestinal electrical activity, and the transcriptional profile of the LM-MP between 21-day-old piglets (just weaned, n=7) and 24-day-old piglets (suffered the most severe weaning stress, n=7). The results showed that 24-day-old piglets exhibited different degrees of diarrhea. A significant increase in the slow-wave frequency in the ileum and colon was observed in 24-day-old piglets, while c-kit expression in the intestinal LM-MPs was significantly decreased, indicating that PWD caused by elevated slow-wave frequency may be associated with loss of c-kit. The real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) showed that intestinal LM-MPs in 24-day-old piglets may undergo inflammation and oxidative stress. Significant increases in 8-hydroxy-2'-deoxyguanosine and decreases in thioredoxin suggest that weaning may lead to DNA damage in the LM-MP of 24-day-old piglets. In addition, activating transcription factor 3 was significantly upregulated, indicating nerve damage in the LM-MP of 24-day-old piglets. The transcriptomic results showed that most of the differentially expressed genes in the ileal LM-MP after weaning were downregulated and closely related to the cell cycle process. Subsequent RT-qPCR analysis showed that the relative expression of p21 was upregulated, while the expression of cyclin A2, cyclin B1, and proliferating cell nuclear antigen was downregulated in the ileal and colonic LM-MP of 24-day-old piglets, suggesting that weaning may inhibit cell proliferation and cause G1/S cell cycle arrest in ileal and colonic LM-MP. In conclusion, weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP, impairing intestinal motility regulation, and ultimately leading to diarrhea in piglets.
Topics: Animals; Swine; Myenteric Plexus; Weaning; Intestines; Diarrhea; Muscles; Intestinal Mucosa
PubMed: 37824029
DOI: 10.1007/s11427-022-2391-x -
Cureus Sep 2023Achalasia, a neurodegenerative disease caused by the progressive destruction of ganglion cells in the myenteric plexus, is accompanied by incomplete relaxation of the... (Review)
Review
Comparison of the Clinical Efficacy, Safety, and Postoperative Outcomes Between Peroral Esophageal Myotomy and Laparoscopic Heller's Myotomy With Fundoplication: A Systematic Review.
Achalasia, a neurodegenerative disease caused by the progressive destruction of ganglion cells in the myenteric plexus, is accompanied by incomplete relaxation of the lower esophageal sphincter. Laparoscopic Heller's myotomy (LHM) coupled with fundoplication has been the gold standard procedure for achalasia. Peroral esophageal myotomy (POEM) has recently gained popularity as it is minimally invasive, has fewer adverse events, and has excellent short-term outcomes. So, we aimed to compare the clinical efficacy, safety, and postoperative outcomes between LHM and POEM. We did a systematic review by following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines for 2020 and exploring research databases such as PUBMED and PMC Central, Google Scholar, and Research Gate. After appropriate screenings, articles relevant to the review were scrutinized based on the eligibility criteria. Quality assessment tools such as the Newcastle-Ottawa Scale (NOS) and the assessment of multiple systematic reviews (AMSTAR) were used to finalize the articles. A total of 11 articles (seven observational studies, two RCTs, and two systematic reviews) were included in the review after a quality check. The study included 2127 patients, classified into 981 for POEM and 1146 for LHM, who had undergone treatment for achalasia. Most of the studies had a follow-up of ≤ two years. Comparing efficacy, POEM had similar results to LHM in terms of Eckardt scores. However, abnormal DeMeester scores were found in POEM. Adverse events were significantly higher in LHM when compared to POEM in terms of safety. Peroral esophageal myotomy also stood out as having a shorter procedure time, a shorter hospital stay, and lesser odds of being a clinical failure. As for postoperative outcomes, despite treatment with proton pump inhibitors, LHM was more effective in preventing the development of esophagitis compared to POEM due to partial fundoplication.Postoperative reflux and the development of esophagitis remain certain with POEM and need to be followed up with more studies with longer follow-ups. However, POEM still stands as a better choice compared to LHM in terms of efficacy and safety.
PubMed: 37818506
DOI: 10.7759/cureus.44877 -
Neurogastroenterology and Motility Nov 2023Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to...
BACKGROUND
Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.
METHODS
Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light microscopy, and myenteric plexus neurochemistry by whole-mount immunostaining.
KEY RESULTS
Regional gastric sampling revealed site-specific differences in contractile patterns and myenteric plexus structure. In neonatal mice, TmSep prolonged gastric emptying. In the forestomach, TmSep increased contractile responses to carbachol, decreased muscularis externa and mucosa thickness, and increased the relative proportion of myenteric plexus nNOS+ neurons. Germ-free conditions did not appreciably alter the structure or function of the neonatal mouse stomach and did not impact the changes caused by TmSep.
CONCLUSIONS AND INFERENCES
A regional sampling approach facilitates site-specific investigations of murine gastric motor physiology and histology to identify site-specific alterations that may impact gastrointestinal function. Delayed gastric emptying in TmSep is associated with a thinner muscle wall, exaggerated cholinergic contractile responses, and increased proportions of inhibitory myenteric plexus nNOS+ neurons in the forestomach. Gut microbes do not profoundly affect the development of the neonatal mouse stomach or the gastric pathophysiology that results from TmSep.
Topics: Mice; Animals; Animals, Newborn; Gastroparesis; Maternal Deprivation; Mice, Inbred C57BL; Stomach; Myenteric Plexus; Disease Models, Animal; Gastric Emptying
PubMed: 37772676
DOI: 10.1111/nmo.14676