Neuronal immaturity in normoganglionic colon from cases of Hirschsprung disease, anorectal malformation, and idiopathic constipation

Miyahara, Katsumi; Kato, Yoshifumi; Seki, Tatsunori; Arakawa, Atsushi; Lane, Geoffrey J.; Yamataka, Atsuyuki

doi:10.1016/j.jpedsurg.2009.07.066

Cited by 19 publications

(4 citation statements)

References 21 publications

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“…Our results showing a decreased level of synapsin 1 in HSCR compared to ARM patients suggest that defects in synapse formation or synaptic transmission between neurons or with gut target cells might occur in HSCR. Previous studies have also reported ENS abnormalities in the ganglionic segment of HSCR patients, such as the overexpression of polysialylated neural cell adhesion molecules, used as a marker of neuronal immaturity 47 . These data, together with our present results, suggest that impaired ENS maturation and connectivity might occur in the normoganglionic gut of HSCR which could contribute to altered gastrointestinal functions, such as motility disturbance often reported in HSCR patients, even after surgery.…”

Section: Discussionmentioning

confidence: 95%

Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease

Gonzalès

Berre‐Scoul

Dariel

et al. 2020

Sci Rep

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Most of the gut functions are controlled by the enteric nervous system (ENS), a complex network of enteric neurons located throughout the wall of the gastrointestinal tract. The formation of ENS connectivity during the perinatal period critically underlies the establishment of gastrointestinal motility, but the factors involved in this maturation process remain poorly characterized. Here, we examined the role of Semaphorin 3A (Sema3A) on ENS maturation and its potential implication in Hirschsprung disease (HSCR), a developmental disorder of the ENS with impaired colonic motility. We found that Sema3A and its receptor Neuropilin 1 (NRP1) are expressed in the rat gut during the early postnatal period. At the cellular level, NRP1 is expressed by enteric neurons, where it is particularly enriched at growth areas of developing axons. Treatment of primary ENS cultures and gut explants with Sema3A restricts axon elongation and synapse formation. Comparison of the ganglionic colon of HSCR patients to the colon of patients with anorectal malformation shows reduced expression of the synaptic molecule synapsin 1 in HSCR, which is inversely correlated with Sema3A expression. Our study identifies Sema3A as a critical regulator of ENS connectivity and provides a link between altered ENS connectivity and HSCR.

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Section: Discussionmentioning

confidence: 95%

Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease

Gonzalès

Berre‐Scoul

Dariel

et al. 2020

Sci Rep

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“…This pattern was also observed in the small intestine subgroups, with 12.9 ± 1.4 cells/mm 2 and 21.3 ± 1.2 cells/mm 2 , and in the rectum subgroups, with 13.4 ± 4.1 cells/mm 2 and 21.9 ± 2.3 cells/mm 2 , for the experimental and control groups respectively. These changes to the ICCs have been correlated with a variety of types of abnormality of intestinal motility, but the results are divergent 14 and their understanding may promote advances in understanding intestinal motility 13 .…”

Section: Evaluation By Immunohistochemical C-kit or Cd-117mentioning

confidence: 99%

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea

et al. 2012

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PURPOSE: The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea. METHODS: Female rats were exposed to ethylenethiourea on the 11th day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively. RESULTS: Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract. CONCLUSION: Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

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“…Several researchers have suggested that this is a self-limiting disease and should be managed with conservative treatment without surgical intervention [ 4 ]. Miyahara [ 12 ] and Venugopal [ 13 ] believe that ganglion cells begin to mature one year after birth, and Feichter et al [ 14 ] thought they are not fully mature until 4 years of age. Therefore, the time of complete maturation of ganglion cells is unclear, and the optimal length of conservative treatment cannot be determined.…”

Section: Discussionmentioning

confidence: 99%

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series

Zhao

Liu

et al. 2022

BMC Surg

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Background Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG. Methods Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored. Results A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31–42), and their median birth weight was 2765 g (range 1300–3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient’s films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1–23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25–100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2–17) and 8 M (range 4–22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up. Conclusion Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.

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Neuronal immaturity in normoganglionic colon from cases of Hirschsprung disease, anorectal malformation, and idiopathic constipation

Cited by 19 publications

References 21 publications

Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease

Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease

Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series

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