Aspects of the human enteric nervous system : A study of the normal development and of Hirschsprung's disease

Sammanfattning: Thirty patients with Hirschsprung's disease (HD) who underwent Rehbein's anterior resection, using a circular stapler to perform the anastomosis, were evaluated retrospectively. The postoperative complication rate and long-term functional outcome were similar to those reported by other investigators using the same and other techniques. This study prompted us to further investigate enteric nervous system (ENS) disorders. The diagnosis of intestinal neuronal dysplasia (IND) has been based on quantitative histological criteria, although normal figures are not well defined. One important purpose of this research was to estimate the density of NADPH diphorase positive neurons (nitric oxide producing) in whole-mount preparations of normal bowel in infants and children of different ages. We evaluated the method and found that NADPH diaphorase histochemistry is a robust staining technique, suitable for tissue obtained at autopsy. Neuron density decreases markedly with increasing age in the myenteric and submucous plexuses.Programmed cell death is important for the development of the central nervous system, but information is scanty as regards the ENS. B-cell leukemia/lymphoma 2 (bcl-2) promotes cell survival and we evaluated bcl-2 expression in enteric ganglia. Bcl-2 is expressed in human gut in the fetus, in children, and in the adult. In aganglionic bowel, bcl-2-immunoreactive neurons are absent. Bcl-2 immunohistochemistry is a good additional technique in the diagnosis of ENS disorders. Interstitial cells of Cajal (ICCs) generate spontaneous pacemaker activity in the gastrointestinal tract. The temporal development of ICCs in the human gut has not previously been described systematically. ICCs, revealed by c-kit immunohistochemistry, are present at 13 weeks of gestation in the human small bowel, but the ICC meshwork does not appear to be developed until the 17th to 18th week of gestation.