Enteric nervous system impairment in gastroschisis

Area of Science:

• Gastroenterology
• Neonatal Surgery
• Developmental Biology

Background:

• Neonates with gastroschisis often experience severe intestinal dysmotility after surgical repair.
• The underlying causes of this dysmotility are not fully understood.
• Impaired development of the enteric nervous system or interstitial cells of Cajal (ICC) network is hypothesized to contribute.

Purpose of the Study:

• To investigate the role of enteric nervous system (ENS) and ICC network development in intestinal dysmotility in a rat model of gastroschisis.
• To compare the maturation of the myenteric plexus and ICCs in gastroschisis versus control and sham-operated groups.

Main Methods:

• Surgically induced gastroschisis in rat fetuses (gestational day 18).
• Assessment of intestinal weight-to-length ratio and wall thickness.
• Immunohistochemistry for neuronal (Hoxb5), glial (GFAP, S100), and ICC (c-kit) markers.
• Morphological assessment and grading of myenteric plexus maturation.

Main Results:

• Gastroschisis was associated with increased intestinal weight-to-length ratio and bowel wall thickness.
• Abnormal myenteric plexus maturation was observed in all gastroschisis specimens, with stages resembling immature fetal development.
• Reduced abundance and abnormal morphology of ICCs were noted in the gastroschisis group.
• Elevated GFAP expression in glial cells was observed in gastroschisis specimens.

Conclusions:

• Delayed ENS maturation and impaired ICC network development are significant contributors to intestinal dysmotility in gastroschisis.
• These findings provide insights into the pathophysiology of post-surgical intestinal dysfunction in neonates with gastroschisis.
• The rat model effectively recapitulates key aspects of human gastroschisis-associated intestinal dysmotility.