Pan-enteric neuropathy and dysmotility are present in a mouse model of short-segment Hirschsprung disease and may contribute to post-pullthrough morbidity.
Dysmotility
Ednrb
Enteric nervous system
Hirschsprung disease
Journal
Journal of pediatric surgery
ISSN: 1531-5037
Titre abrégé: J Pediatr Surg
Pays: United States
ID NLM: 0052631
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
17
02
2020
revised:
14
03
2020
accepted:
06
04
2020
pubmed:
18
5
2020
medline:
25
6
2021
entrez:
17
5
2020
Statut:
ppublish
Résumé
Hirschsprung disease (HSCR) is characterized by distal intestinal aganglionosis. While surgery is lifesaving, gastrointestinal (GI) motility disorders persist in many patients. Our objective was to determine whether enteric nervous system (ENS) abnormalities exist in the ganglionated portions of the GI tract far proximal to the aganglionic region and whether these are associated with GI dysmotility. Using Ednrb-null mice, a model of HSCR, immunohistochemical analysis was performed to evaluate quantitatively ENS structure in proximal colon, small intestine, and stomach. Gastric emptying and intestinal transit were measured in vivo and small and large bowel contractility was assessed by spatiotemporal mapping ex vivo. Proximal colon of HSCR mice had smaller ganglia and decreased neuronal fiber density, along with a marked reduction in migrating motor complexes. The distal small intestine exhibited significantly fewer ganglia and decreased neuronal fiber density, and this was associated with delayed small intestinal transit time. Finally, in the stomach of HSCR mice, enteric neuronal packing density was increased and gastric emptying was faster. ENS abnormalities and motility defects are present throughout the ganglionated portions of the GI tract in Ednrb-deficient mice. This may explain the GI morbidity that often occurs following pull-through surgery for HSCR.
Identifiants
pubmed: 32414519
pii: S0022-3468(20)30260-8
doi: 10.1016/j.jpedsurg.2020.04.002
pmc: PMC7572464
mid: NIHMS1585522
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
250-256Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK103785
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
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