Selective chemical ablation of the enteric plexus in mice |
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Authors: | Yoneda Akihiro Shima Hideki Nemeth Laszlo Oue Takaharu Puri Prem |
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Institution: | (1) Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland, IE |
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Abstract: | Although genetically aganglionic mice such as piebald lethal and lethal spotted mice exhibit striking similarities to the
human condition of Hirschsprung's disease (HD), the aganglionic segment is very short and always located in the distal part
of the rectum. Topical application of benzalkonium chloride (BAC) to the rectum of rats has been reported to result in segmental
aganglionosis. To induce chemical ablation of the enteric plexus in mice to produce an aperistaltic narrow segment simulating
HD, 32 mice were divided into three groups: (1) abdominal (n=12), for sigmoid colon treatment; (2) rectal (n=10), for rectum
treatment; and (3) controls (n=10). For groups 1 and 2, 0.1% BAC was applied to a 1-cm serosal surface of the bowel for 15
min. In the controls, isotonic saline was applied in this fashion. A detailed histologic examination was performed using hematoxylin
and eosin staining and acetylcholinesterase histochemistry. Ten animals (9 in group 1 and 1 in group 2) died 1 to 9 weeks
after BAC treatment. Autopsy revealed a narrow segment of bowel at the site of BAC treatment and marked dilatation of the
bowel proximal to the narrow segment. The remaining animals were killed 12 weeks after BAC treatment. Histologic examination
demonstrated normal myenteric and submucous plexuses in the controls, whereas there was a total lack of innervation in the
BAC-treated segments.
Topical application of BAC thus successfully produced a narrow aganglionic segment of bowel in normal mice. This model provides
the basis for future studies to investigate the pathophysiology of HD and megacolon and for comparison with genetically aganglionic
mice.
Accepted: 18 April 2001 |
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Keywords: | Aganglionosis Animal model Hirschsprung's disease Benzalkonium chloride |
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