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Published in: Pediatric Surgery International 1/2023

01-12-2023 | Original Article

High intestinal vascular permeability in a murine model for Hirschsprung’s disease: implications for postoperative Hirschsprung-associated enterocolitis

Authors: Kazuto Suda, Shunsuke Yamada, Katsumi Miyahara, Naho Fujiwara, Seitaro Kosaka, Kumpei Abe, Shogo Seo, Shinji Nakamura, Geoffrey J. Lane, Atsuyuki Yamataka

Published in: Pediatric Surgery International | Issue 1/2023

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Abstract

Purpose

Intestinal vascular permeability (VP) in a murine model for Hirschsprung’s disease (HD) and postoperative Hirschsprung-associated enterocolitis (HAEC) were investigated.

Methods

Intestinal VP was determined using a Miles assay using 1% Evans blue injected into a superficial temporal vein of newborn endothelin receptor-B KO HD model (KO) and syngeneic wild-type (WT) mice (n = 5, respectively). Extravasated Evans blue in normoganglionic ileum (Ng-I), normoganglionic proximal colon (Ng-PC) and aganglionic distal colon (Ag-DC) was quantified by absorbance at 620 nm. Quantitative polymerase chain reaction (qPCR) for Vascular Endothelial Growth Factor A (VEGF-A), VEGF-B, CDH5, SELE and CD31, and immunofluorescence for CD31 were performed.

Results

VP was significantly higher in Ng-I, Ng-PC, and Ag-DC from KO than WT (p < 0.01, p < 0.05, and p < 0.05, respectively). qPCR demonstrated upregulated VEGF-A in Ng-I and Ag-DC, VEGF-B in Ng-I, and SELE in Ng-I and Ng-PC (p < 0.05, p < 0.05, p < 0.05, p < 0.01 and p < 0.05, respectively), and downregulated CDH5 in Ng-I and Ng-PC from KO (p < 0.05, respectively). Expression of CD31 mRNA in Ng-I and Ag-DC from KO was significantly higher on qPCR (p < 0.05) but differences on immunofluorescence were not significant.

Conclusions

VP may be etiologic for postoperative HAEC throughout the intestinal tract even after excision of aganglionic bowel.
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Metadata
Title
High intestinal vascular permeability in a murine model for Hirschsprung’s disease: implications for postoperative Hirschsprung-associated enterocolitis
Authors
Kazuto Suda
Shunsuke Yamada
Katsumi Miyahara
Naho Fujiwara
Seitaro Kosaka
Kumpei Abe
Shogo Seo
Shinji Nakamura
Geoffrey J. Lane
Atsuyuki Yamataka
Publication date
01-12-2023
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Surgery International / Issue 1/2023
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI
https://doi.org/10.1007/s00383-022-05308-7

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