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

Abstract Purpose 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. Methods 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. Results 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 (p < 0.01) and day 10 (p < 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 (p = 0.046). Nestin and S100 double-staining showed an increased expression of nestin around the anastomotic wound. Conclusion 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.

[1]  N. Kessaris,et al.  Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury. , 2011, The Journal of clinical investigation.

[2]  S. Morrison,et al.  Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut. , 2011, The Journal of clinical investigation.

[3]  S. Copray,et al.  Plasticity and Neural Stem Cells in the Enteric Nervous System , 2009, Anatomical record.

[4]  J. Furness,et al.  The enteric nervous system: normal functions and enteric neuropathies , 2008, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[5]  E. Benarroch,et al.  Enteric nervous system , 2007, Neurology.

[6]  Hong-jun Zhang,et al.  Interstitial cells of Cajal could regenerate and restore their normal distribution after disrupted by intestinal transection and anastomosis in the adult guinea pigs , 2006, Virchows Archiv.

[7]  A. Burns,et al.  Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract , 2005, Cell and Tissue Research.

[8]  S. Ward,et al.  Intestinal surgical resection disrupts electrical rhythmicity, neural responses, and interstitial cell networks. , 2004, Gastroenterology.

[9]  K. Boheler,et al.  Nestin expression – a property of multi-lineage progenitor cells? , 2004, Cellular and Molecular Life Sciences CMLS.

[10]  M. Hanani,et al.  Regeneration of myenteric plexus in the mouse colon after experimental denervation with benzalkonium chloride , 2003, The Journal of comparative neurology.

[11]  S. Morrison,et al.  Neural Crest Stem Cells Persist in the Adult Gut but Undergo Changes in Self-Renewal, Neuronal Subtype Potential, and Factor Responsiveness , 2002, Neuron.

[12]  S. Schiffmann,et al.  Distribution of the intermediate filament nestin in the muscularis propria of the human gastrointestinal tract , 2002, Cell and Tissue Research.

[13]  M. Blennerhassett,et al.  Damage to the enteric nervous system in experimental colitis. , 1999, The American journal of pathology.

[14]  A. Surprenant,et al.  Somatostatin‐mediated inhibitory postsynaptic potential in sympathetically denervated guinea‐pig submucosal neurones. , 1993, The Journal of physiology.

[15]  M. Gershon,et al.  Colonization of the chick gut by progenitors of enteric serotonergic neurons: distribution, differentiation, and maturation within the gut. , 1980, Developmental biology.

[16]  J. Dunn,et al.  Regeneration of enteric ganglia in mechanically lengthened jejunum after restoration into intestinal continuity. , 2013, Journal of pediatric surgery.

[17]  得居 和義 Progressive reorganization of the myenteric plexus during one year following reanastomosis of the ileum of the guinea pig , 1994 .