Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease

Autor: Anne Dariel, Lucie Grynberg, Marie Auger, Chloé Lefèvre, Tony Durand, Philippe Aubert, Catherine Le Berre-Scoul, Aurélien Venara, Etienne Suply, Marc-David Leclair, Philine de Vries, Guillaume Levard, Benoit Parmentier, Guillaume Podevin, Françoise Schmitt, Véronique Couvrat, Sabine Irtan, Erik Hervieux, Thierry Villemagne, Hubert Lardy, Carmen Capito, Cécile Muller, Sabine Sarnacki, Jean-François Mosnier, Louise Galmiche, Pascal Derkinderen, Hélène Boudin, Charlène Brochard, Michel Neunlist
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-020-78340-z
Popis: Abstract In Hirschsprung’s disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications (p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC (p = 0.016; p = 0.009) and HSCR without complications (p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR.
Databáze: Directory of Open Access Journals
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