Intrinsic Myenteric Denervation: A New Model to Increase the Intestinal Absorptive Surface in Short-Bowel Syndrome

Garcia, Sérgio Britto; Kawasaky, M.C.; Silva, J.C.F.; Garcia-Rodrigues, A.C.; Borelli-Bovo, Tiago; Iglesias, Antonio; Zucoloto, Sérgio

doi:10.1006/jsre.1999.5670

Cited by 23 publications

(24 citation statements)

References 12 publications

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“…In this context, several prior observations suggest that components of the ENS may have an inhibitory effect on intestinal adaptation. For example, destruction of the ENS with benzalkonium chloride causes enhanced adaptation after SBR that closely mimics our results (8,14). Benzalkonium chloride-induced bowel denervation, however, increases crypt depth and villus height in rats, even without SBR (8), whereas Retϩ/Ϫ have similar morphology to WT animals in the absence of SBR.…”

Section: Discussionsupporting

confidence: 84%

Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection

Hitch

Leinicke

Wakeman

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Intestinal adaptation is an important compensatory response to massive small bowel resection (SBR) and occurs because of a proliferative stimulus to crypt enterocytes by poorly understood mechanisms. Recent studies suggest the enteric nervous system (ENS) influences enterocyte proliferation. We, therefore, sought to determine whether ENS dysfunction alters resection-induced adaptation responses. Ret+/- mice with abnormal ENS function and wild-type (WT) littermates underwent sham surgery or 50% SBR. After 7 days, ileal morphology, enterocyte proliferation, apoptosis, and selected signaling proteins were characterized. Crypt depth and villus height were equivalent at baseline in WT and Ret+/- mice. In contrast after SBR, Ret+/- mice had longer villi (Ret+/- 426.7 ± 46.0 μm vs. WT 306.5 ± 7.7 μm, P < 0.001) and deeper crypts (Ret+/- 119 ± 3.4 μm vs. WT 82.4 ± 3.1 μm, P < 0.001) than WT. Crypt enterocyte proliferation was higher in Ret+/- (48.8 ± 1.3%) than WT (39.9 ± 2.1%; P < 0.001) after resection, but apoptosis rates were similar. Remnant bowel of Ret+/- mice also had higher levels of glucagon-like peptide 2 (6.2-fold, P = 0.005) and amphiregulin (4.6-fold, P < 0.001) mRNA after SBR, but serum glucagon-like peptide 2 protein levels were equal in WT and Ret+/- mice, and there was no evidence of increased c-Fos nuclear localization in submucosal neurons. Western blot confirmed higher crypt epidermal growth factor receptor (EGFR) protein levels (1.44-fold; P < 0.001) and more phosphorylated EGFR (2-fold; P = 0.003) in Ret+/- than WT mice after SBR. These data suggest that Ret heterozygosity enhances intestinal adaptation after massive SBR, likely via enhanced EGFR signaling. Reducing Ret activity or altering ENS function may provide a novel strategy to enhance adaptation attenuating morbidity in patients with short bowel syndrome.

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Section: Discussionsupporting

confidence: 84%

Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection

Hitch

Leinicke

Wakeman

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Although the levels of GLP-1, a peptide hormone that is cosynthesized and cosecreted with GLP-2 (14), were normal in the PI3-K␥ null mice, further studies are clearly required to determine whether adaptive or PI3-K␥-mediated changes in other intestinal hormones have occurred in these animals. Finally, delayed transit of nutrients through the gut can also enhance small intestinal growth (20). However, PI3-K␥ KO animals were found to have normal transit times compared with WT mice, suggesting that this cannot account for the enhanced basal small intestinal growth in these animals.…”

Section: Discussionmentioning

confidence: 91%

“…4, A and B), the putative "clonogenic stem cell region" of the crypt (29). However, differences among the different groups of animals were observed in positions [11][12][13][14][15][16][17][18][19][20], which correspond to the "rapidly proliferating transit zone" (29). PBS-treated KO mice were found to have greater numbers of proliferating cells in this region of the crypt compared with PBS-treated WT animals (by 50%, P Ͻ 0.05; Fig.…”

Section: Expression Of P110␥mentioning

confidence: 99%

Role of phosphatidylinositol-3 kinase-γ in the actions of glucagon-like peptide-2 on the murine small intestine

Anini¹,

Izzo²,

Oudit³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Serosal cationic surfactant BCl application has been effective in producing aganglionic segments in the gastrointestinal tract of various animal models; the model was first described by Sato et al [6], and has been very useful in morphological and functional studies of different segments of the gastrointestinal tract, as reported for the esophagus, stomach, duodenum, jejunum, ileum and colon [9][10][11]. This cationic surfactant in appropriate doses selectively destroys nerve cell membranes without harming muscular tissue.…”

Section: Discussionmentioning

confidence: 99%

Effects of Benzalkonium Chloride Application on the Rat Bladder

Kaya

Baba²,

Deniz³

et al. 2005

Urol Int

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Aim: To establish a new bladder denervation model for bladder augmentation, using benzalkonium chloride (BCl) treatment, and to characterize the normal and treated rat bladder both urodynamically and immunohistochemically. Methods: Adult Wistar rats were divided into two groups, and the bladders were treated with a local application of 0.3% BCl for 30 min in the denervation group and saline in the control group. Before and at the 8th week after treatment, cystometry was performed in all rats, and results were recorded. The bladders were removed and whole-mount sections were prepared, and also evaluated by immunohistochemistry. Results: BCl-treated rats showed a significant increase in bladder capacity (p < 0.05), but no significant change was observed in other cystometric parameters (p > 0.05) when compared with control rats. Immunohistochemistry revealed none or very few nerve fibers within the BCl-treated bladders. Conclusions: The present study showed that denervation caused by BCl is useful for augmentation of the rat bladder. Bladder capacity was increased by the local application of BCl without impairing bladder functions. This method with a better understanding of the effects of BCl may be useful for augmentation in patients who have neurogenic bladder with low capacity.

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Intrinsic Myenteric Denervation: A New Model to Increase the Intestinal Absorptive Surface in Short-Bowel Syndrome

Cited by 23 publications

References 12 publications

Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection

Ret heterozygous mice have enhanced intestinal adaptation after massive small bowel resection

Role of phosphatidylinositol-3 kinase-γ in the actions of glucagon-like peptide-2 on the murine small intestine

Effects of Benzalkonium Chloride Application on the Rat Bladder

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