Murine model of Hirschsprung-associated enterocolitis II: Surgical correction of aganglionosis does not eliminate enterocolitis.

Journal of Pediatric Surgery
Lifu ZhaoPhilip K Frykman

Abstract

Hirschsprung disease (HD) results from aganglionosis of the colon, is linked to acute and chronic enterocolitis (known as Hirschsprung-associated enterocolitis) despite successful corrective surgery, and can lead to bacteremia and even death. The genetic and molecular mechanisms underlying these disorders are largely unknown. We developed a microsurgical corrective pull-through procedure in mice, and applied that to Ednrb(-/-) mice, which manifest aganglionic megacolon that is very similar to HD. Wild-type littermates (Ednrb(+/+)) also underwent identical surgery. At prespecified time points postoperatively, mice were sacrificed, and histopathologic analyses of intestinal inflammation were performed. Mice of both genotypes were sacrificed after the postoperative recovery period to determine if corrective surgery itself caused inflammation. Stooling patterns were assessed as well to determine if intestinal function normalized after surgery. There was no difference in histopathological enterocolitis scores after recovery from surgery. Stooling patterns in Ednrb(-/-) and Ednrb(+/+) mice were similar postoperatively, suggesting normalization of intestinal function. However, with time, approximately 40% of Ednrb(-/-) mice developed ...Continue Reading

Citations

Jul 17, 2013·Current Gastroenterology Reports·Elizabeth M PontarelliChristopher P Gayer
Jan 1, 2010·Journal of Neuroparasitology·Linda A Jelicks
Jul 13, 2013·Journal of Pediatric Surgery·Amit AggarwalOliver J Muensterer
Jan 20, 2016·Pediatric Surgery International·Ankush Gosain
Dec 22, 2015·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·R HottaA M Goldstein
May 26, 2012·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·N L WardA M Goldstein
Oct 2, 2015·Journal of Neurogastroenterology and Motility·Lincon A StampJohn B Furness
Apr 7, 2015·Cellular and Molecular Gastroenterology and Hepatology·Melissa A MusserE Michelle Southard-Smith
May 7, 2015·Current Opinion in Pediatrics·Ankush Gosain, Adam S Brinkman
Aug 19, 2020·The Journal of Clinical Investigation·Xuyong ChenJiexiong Feng

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