Developmental changes of the adrenergic network in the myenteric plexus of the porcine small bowel.

Knowledge about the foetal development of the normal enteric nervous system (ENS) is crucial for the understanding of congenital and acquired functional abnormalities of the gut. The ENS is the largest and most complex division of the peripheral nervous system and consists of intrinsic and extrinsic components. Although previous studies have described sympathetic innervation of the myenteric plexus, little is known regarding its age-related changes. The aim of this study was to investigate the age-related changes in the sympathetic innervation of the myenteric plexus. Whole mount and paraffin sections of the small bowel specimens from six different age groups (60 and 90 days gestation; newborn; 4 and 12 weeks old; and adult) were stained using tyrosine hydroxylase immunohistochemistry. Specimens were then analysed using fluorescence and laser scanning microscopy in detail. The tyrosine hydroxylase positive nerve fibres were first seen within the myenteric plexus at 90 days of gestation (E90). There was a significant increase in nerve fibres and varicosities observed from E90 to 12 weeks of age and stabilisation thereafter. The degree of varicosities around the ganglia, clearly seen on the whole-mount preparations, was also noted to increase up to 12 weeks of age, after which time there was no general variation noted into adulthood. Our findings show, for the first time, that sympathetic innervation of the myenteric plexus starts in the last quarter of gestation and continues till 12 weeks of age. Segmental sympathetic denervation, following bowel resection and anastomosis, during this developmental period may explain the motility dysfunction seen in newborn infants operated for necrotising enterocolitis, bowel atresia and Hirschsprung's disease.