Enteric Nervous System Impairment in Gastroschisis

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

Outcomes in infants with prenatally diagnosed gastroschisis and planned preterm delivery

“…As the pregnancy with gastroschisis progresses, the bowel usually becomes coated in an inflammatory fibrinous peel, resulting in thickening of the bowel wall, decreased bowel motility and possible luminal obstruction [4][5][6]. Several studies have demonstrated neuronal immaturity in animal models of gastroschisis that might explain the postnatal dysmotility observed in some of the patients with gastroschisis [43][44][45].…”

Advances in Evaluation of Chronic Diarrhea in Infants

“…Disorders such as gastroschisis 41 may result in diarrhea by various mechanisms, including impaired motility, 42 surgical formation of ostomies that shorten bowel length, or bacterial overgrowth. Patients with gastroschisis can also acquire SBS as a result of volvulus that can occur before or after birth.…”

To Wean or Not to Wean: The Role of Autologous Reconstructive Surgery in the Natural History of Pediatric Short Bowel Syndrome on Behalf of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP)

“…It has been suggested that gastroschisis may be unfavored in terms of adaptation by the underlying severe dysmotility [ 63 ]. In animal models, gastroschisis is associated with hypertrophy and hyperplasia of both the circular and longitudinal muscle layers [ 64 , 65 ] and to a late differentiation of the intestinal cells of Cajal [ 66 ], which can all explain the dysmotility. Gastroschisis accounted for one third of the indications of AGIR and STEP and that suggests that such patients may be more prone to develop dilation as a consequence of dysmotility, than other primary diagnoses of SBS.…”