Regeneration of enteric ganglia in mechanically lengthened jejunum after restoration into intestinal continuity

Jabaji, Ziyad; Stark, Rebecca; Dunn, James C.Y.

doi:10.1016/j.jpedsurg.2012.10.027

Cited by 17 publications

(7 citation statements)

References 27 publications

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“…The extent of muscularis hypertrophy we observed after jejunal treatment with BAC further substantiates our colleagues' prior observations. [28][29][30] In combination with segmental isolation, we observed BAC denervation produced a 90% increase in muscularis thickness. Our observations of jejunal isolation and denervation suggest substantial hypertrophy develops to counteract the radial force generated by accumulating mucus within the isolated segment; however, the hypertrophy we observed over time had no discernable predilection for either the circular or longitudinal smooth muscle layer.…”

Section: Discussionmentioning

confidence: 75%

A Novel In Vivo Model of Permanent Intestinal Aganglionosis

Wagner

Sullins

Chiang

et al. 2014

Journal of Surgical Research

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Background-Enteric neuromuscular disease is characteristic of several disease states, including Hirschsprung's disease, esophageal achalasia, Chagas disease, and gastroparesis. Medical therapy for these conditions is limited, and surgical intervention may incur significant morbidity. Alternatively, transplantation of neural progenitor cells may regenerate enteric ganglia. Existing aganglionosis model systems are limited by swift animal demise or by spontaneous regeneration of native ganglia. We propose a novel protocol to induce permanent aganglionosis in a segment of rat jejunum, which may serve as an experimental transplantation target for cellular therapy. Materials and Methods-This protocol was performed in 17 adult female Sprague-Dawley rats. A laparotomy was performed and a one-centimeter segment of jejunum was isolated from continuity. Among 14 rats, the isolated segments were treated with benzalkonium chloride (BAC) for 20 minutes to induce aganglionosis. Jejunal segment isolation was performed without BAC treatment in three rats. The animals were euthanized at post-treatment days 21-166. Muscle layer diameter was compared among normal, isolated, and BAC-treated isolated jejunal segments. The presence of jejunal ganglia was documented by immunohistochemical staining (IHC) for beta-III tubulin (TUJ1) and S100, markers of neuronal and glial cell lineages, respectively. Results-Ganglia were identified by IHC in normal and isolated jejunal segments. Isolated segments had significantly hypertrophied smooth muscle layers compared to normal jejunum

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Section: Discussionmentioning

confidence: 75%

A Novel In Vivo Model of Permanent Intestinal Aganglionosis

Wagner

Sullins

Chiang

et al. 2014

Journal of Surgical Research

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show abstract

“…28-30 In combination with segmental isolation, we observed BAC denervation produced a 90% increase in muscularis thickness. Our observations of jejunal isolation and denervation suggest substantial hypertrophy develops to counteract the radial force generated by accumulating mucus within the isolated segment; however, the hypertrophy we observed over time had no discernable predilection for either the circular or longitudinal smooth muscle layer.…”

Section: Discussionmentioning

confidence: 76%

A novel in vivo model of permanent intestinal aganglionosis

Wagner

Sullins

Dunn

2014

Journal of Surgical Research

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Background Enteric neuromuscular disease is characteristic of several disease states, including Hirschsprung’s disease, esophageal achalasia, Chagas disease, and gastroparesis. Medical therapy for these conditions is limited, and surgical intervention may incur significant morbidity. Alternatively, transplantation of neural progenitor cells may regenerate enteric ganglia. Existing aganglionosis model systems are limited by swift animal demise or by spontaneous regeneration of native ganglia. We propose a novel protocol to induce permanent aganglionosis in a segment of rat jejunum, which may serve as an experimental transplantation target for cellular therapy. Materials and Methods This protocol was performed in 17 adult female Sprague-Dawley rats. A laparotomy was performed and a one-centimeter segment of jejunum was isolated from continuity. Among 14 rats, the isolated segments were treated with benzalkonium chloride (BAC) for 20 minutes to induce aganglionosis. Jejunal segment isolation was performed without BAC treatment in three rats. The animals were euthanized at post-treatment days 21-166. Muscle layer diameter was compared among normal, isolated, and BAC-treated isolated jejunal segments. The presence of jejunal ganglia was documented by immunohistochemical staining (IHC) for beta-III tubulin (TUJ1) and S100, markers of neuronal and glial cell lineages, respectively. Results Ganglia were identified by IHC in normal and isolated jejunal segments. Isolated segments had significantly hypertrophied smooth muscle layers compared to normal jejunum (diameter 343 ± 53 μm vs 211 ± 37 μm, P<0.0001). BAC-treated jejunal segments had no IHC evidence of ganglionic structures. Aganglionosis was persistent in all specimens up to 166 days post-treatment. Conclusions The exclusion of a jejunal segment from continuity and concurrent treatment with BAC results in an effective, reproducible, and permanent model of aganglionosis. Muscular hypertrophy and aganglionosis in the isolated jejunal segment make it an ideal recipient site for transplantation of neuroglial precursor cells.

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“…Degenerative and regenerative changes after surgical interruption of the ENS have been reported, [12][13][14][15] but until now no studies evaluating specific differences in the myenteric and submucosal plexus have been published. In this study, we found that myenteric ganglia appeared to recover faster as ganglia count had normalized after 10 days.…”

Section: Discussionmentioning

confidence: 99%

Regenerative Capacity of the Enteric Nervous System after Ileoileal Anastomoses in a Rat Model

et al. 2016

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The aim of the study was to investigate the regeneration and migration of neuronal progenitor cells of the enteric nervous system during wound healing after intestinal anastomosis in the rat ileum. Experiments were performed in a rat model of ileoileal anastomosis. Rats were humanely killed on day 2 or day 10 after anastomosis, and the anastomotic region was compared with ileum of healthy rats. Immunofluorescent staining was performed with protein gene product 9.5, nestin, and S100 antibodies. Ganglia of the anastomotic region in both the myenteric and submucosal plexus were counted, and their diameters were measured and compared between groups. Analysis of number and diameter of ganglia in both myenteric and submucosal plexus showed individual alterations as a reaction to the surgical manipulation. Significantly less ganglia were found in the submucosal plexus in the operated groups at both day 2 ( < 0.01) and day 10 ( < 0.01) than in the control group. In the myenteric plexus in the operated group, there was a difference in the number of ganglia at day 2, but ganglia count had recovered at day 10 and was not significantly different from the control group. However, the diameter of ganglia in the myenteric plexus still significantly decreasing on day 10 after surgery than in the control group ( = 0.046). Nestin and S100 double-staining showed an increased expression of nestin around the anastomotic wound. Our findings suggest a regenerative potential of the enteric nervous system after the surgical ileoileal anastomosis. The myenteric plexus appears to recover faster than the submucosal plexus. This recovery might be driven by nestin-positive neuronal progenitor cells.

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Regeneration of enteric ganglia in mechanically lengthened jejunum after restoration into intestinal continuity

Cited by 17 publications

References 27 publications

A Novel In Vivo Model of Permanent Intestinal Aganglionosis

A Novel In Vivo Model of Permanent Intestinal Aganglionosis

A novel in vivo model of permanent intestinal aganglionosis

Regenerative Capacity of the Enteric Nervous System after Ileoileal Anastomoses in a Rat Model

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