Abstract
Introduction After surgical repair of gastroschisis, most neonates exhibit severe intestinal dysmotility.
We hypothesized that impaired development of the enteric nervous system or interstitial
cells of Cajal (ICC) network contributes to impaired intestinal motility in gastroschisis.
We evaluated this hypothesis in a rat model of gastroschisis.
Material and Methods Gastroschisis was created surgically in rat fetuses on gestational day 18, under
general anesthesia, and small bowel was harvested on day 22. Intestinal weight-to-length
(IW/L) ratio, and small-bowel wall thickness were assessed. Specimens were processed
for hematoxylin-eosin staining or immunohistochemistry with specific markers for neuronal
cells (Hoxb5), glial cells (GFAP, S100), and ICCs (c-kit). Myenteric plexus maturation
was assessed morphologically and compared with sham and control fetuses. Stage of
development of the myenteric plexus was graded from 1 (mature) to 3 (very immature)
comparatively with specimens from E16 to E22 control fetuses.
Results Compared with sham-operated or control fetuses, gastroschisis was associated with
increases in mean intestinal weight/intestinal length (IW/L) ratio, and mean thicknesses
of the total, muscular, and submucosal layers of the small-bowel wall. The myenteric
plexus were present in the small bowel from fetuses with gastroschisis, however all
exhibited abnormal myenteric plexus maturation. Thus, of the gastroschisis fetuses,
55% had an aspect similar to the immature myenteric plexus of E19-E20 fetuses and
45% to the very immature mesenteric plexus observed in E16-E18 fetuses. When compared
with sham and control groups, ICCs were less abundant in eviscerated small bowel in
the gastroschisis group and often exhibited weak c-kit staining or an abnormally round
shape without branches. Hoxb5, a marker for enteric neuroblasts and neuronal precursors,
was expressed similarly in myenteric plexuses in all groups. S100 or GFAP staining
showed the presence of glial cells within the myenteric plexuses in all groups. The
S100 expression level was similar in all groups. In contrast, the GFAP expression
level was higher in the gastroschisis group than in the sham and control groups.
Conclusion Our results suggest that delayed maturation of the enteric nervous system combined
with impaired ICC network development may largely explain the intestinal dysmotility
seen in neonates with gastroschisis.
Keywords
gastroschisis - enteric nervous system - interstitial cells of Cajal - experimental
models
