Three-dimensional morphology of gut innervation in total intestinal aganglionosis using whole-mount preparation

Background: Total intestinal aganglionosis (TIA) is a rare form of Hirschsp rung's disease (HD). The aim of this study was to examine the 3-dimensional morphology of the myentric plexus of the entire gastrointestinal tract in a newborn with total intestinal aganglionosis. Methods: Whole-mount preparations were made of the entire gastrointestinal tract using NADPH-diaphorase histochemistry and c-kit (a marker of intersti tial cells of Cajal) immunohistochemistry. Results: Whole-mount preparations of the esophagus, stomach, and duodenum s howed 3-dimensional morphology of the myenteric plexus forming a meshlike n etwork of nerve fibers, connected to each other and to ganglia. There were large numbers of NADPH-diaphrase-positive nerve fibers between the muscle f ibers in the circular muscle layer. In esophagus, stomach, and duodenum, c- kit-positive interstitial cells of Cajal (ICC) formed a 3-dimensional netwo rk between the two muscle layers and also were abundant within the circular muscle layer. In the jejunum, ileum, and colon, the myenteric plexus was a bsent and was replaced by hypertrophic nerve bundles that stained weakly wi th NADPH-diaphrase. Circular muscle layer completely lacked NADPH-diaphrase -positive nerve fibers. The c-kit-positive ICCs in the jejunum, ileum, and colon were sparse and localized mainly around the nerve trunks between the circular and longitudinal muscle layers. Conclusions: Whole-mount preparation is an elegant 3-dimensional technique in which the relationship of branching and interconnecting nerve fibers to each other and to muscle can be seen clearly. Absence of myenteric plexus, lack of nitrergic innervation, and depletion of interstitial cells of Cajal in the bowel wall throughout the small and large bowel contribute to the i nability of the smooth muscle to relax, thereby causing lack of peristalsis in TIA. Copyright (C) 2001 by W.B. Saunders Company.