Skip to main content

Advertisement

SpringerLink
Log in

Enteric nervous system and developmental abnormalities in childhood

  • Review Article
  • Published:
Pediatric Surgery International Aims and scope Submit manuscript

Abstract

ENS consists of a complex network of neurons, organised in several plexuses, which interact by means of numerous neurotransmitters. It is capable of modulating the intestinal motility, exocrine and endocrine secretions, microcirculation and immune and inflammatory responses within the gastrointestinal tract, independent of the central nervous system. Though the embryological development of various plexuses are completed by mid-way of gestation, the maturation of neurons and nerve plexuses appear to continue well after birth. Therefore, any histological or functional abnormalities related to the gastrointestinal function must be investigated with the ongoing maturational processes in mind.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Furness J (2006) The enteric nervous system. Blackwell, Massachusetts

    Google Scholar 

  2. Gershon MD (1999) The enteric nervous system: a second brain. Hosp Pract (Minneap) 34:31–32, 35–38, 41–32 passim

  3. Goyal RK, Hirano I (1996) The enteric nervous system. N Engl J Med 334:1106–1115

    PubMed  CAS  Google Scholar 

  4. Rolle U, Nemeth L, Puri P (2002) Nitrergic innervation of the normal gut and in motility disorders of childhood. J Pediatr Surg 37:551–567

    PubMed  Google Scholar 

  5. Costa M, Brookes SJ, Hennig GW (2000) Anatomy and physiology of the enteric nervous system. Gut 47 Suppl 4: iv15–19; discussion iv26

    Google Scholar 

  6. JB Furness MC (1987) The enteric nervous system. Churchill Livingstone, New York

  7. Gabella G (1984) Size of neurons and glial cells in the intramural ganglia of the hypertrophic intestine of the guinea-pig. J Neurocytol 13:73–84

    PubMed  CAS  Google Scholar 

  8. Ruhl A, Franzke S, Stremmel W (2001) IL-1beta and IL-10 have dual effects on enteric glial cell proliferation. Neurogastroenterol Motil 13:89–94

    PubMed  CAS  Google Scholar 

  9. Puri P, Shinkai T (2004) Pathogenesis of Hirschsprung’s disease and its variants: recent progress. Semin Pediatr Surg 13:18–24

    PubMed  Google Scholar 

  10. Gershon MD, Chalazonitis A, Rothman TP (1993) From neural crest to bowel: development of the enteric nervous system. J Neurobiol 24:199–214

    PubMed  CAS  Google Scholar 

  11. Yntema CL, Hammond WS (1954) The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo. J Comp Neurol 101:515–541

    PubMed  CAS  Google Scholar 

  12. Bates M (2002) Development of the enteric nervous system. Clin Perinatol 29:97–114

    PubMed  CAS  Google Scholar 

  13. Young HM, Hearn CJ, Newgreen DF (2000) Embryology and development of the enteric nervous system. Gut 47 Suppl 4: iv12–14; discussion iv26

    Google Scholar 

  14. Roman V, Bagyanszki M, Krecsmarik M, Horvath A, Resch BA, Fekete E (2004) Spatial pattern analysis of nitrergic neurons in the developing myenteric plexus of the human fetal intestine. Cytometry A 57:108–112

    PubMed  CAS  Google Scholar 

  15. Le Douarin NM, Teillet MA (1973) The migration of neural crest cells to the wall of the digestive tract in avian embryo. J Embryol Exp Morphol 30:31–48

    PubMed  CAS  Google Scholar 

  16. Pomeranz HD, Gershon MD (1990) Colonization of the avian hindgut by cells derived from the sacral neural crest. Dev Biol 137:378–394

    PubMed  CAS  Google Scholar 

  17. Burns AJ, Douarin NM (1998) The sacral neural crest contributes neurons and glia to the post-umbilical gut: spatiotemporal analysis of the development of the enteric nervous system. Development 125:4335–4347

    PubMed  CAS  Google Scholar 

  18. Caniano DA, Ormsbee HS 3rd, Polito W, Sun CC, Barone FC, Hill JL (1985) Total intestinal aganglionosis. J Pediatr Surg 20:456–460

    PubMed  CAS  Google Scholar 

  19. Furness J, Clere N, Vogalis F, Stebbing MJ (2003) The enteric nervous system and its extrinsic connections. Lippincot Williams, Philadelphia

    Google Scholar 

  20. Brandt CT, Tam PK, Gould SJ (1996) Nitrergic innervation of the human gut during early fetal development. J Pediatr Surg 31:661–664

    PubMed  CAS  Google Scholar 

  21. Montgomery RK, Mulberg AE, Grand RJ (1999) Development of the human gastrointestinal tract: twenty years of progress. Gastroenterol116:702–731

    CAS  Google Scholar 

  22. Taraviras S, Pachnis V (1999) Development of the mammalian enteric nervous system. Curr Opin Genet Dev 9:321–327

    PubMed  CAS  Google Scholar 

  23. Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380–383

    PubMed  CAS  Google Scholar 

  24. Kusafuka T, Puri P (1997) The RET proto-oncogene: a challenge to our understanding of disease pathogenesis. Pediatr Surg Int 12:11–18

    PubMed  CAS  Google Scholar 

  25. Martucciello G, Ceccherini I, Lerone M, Jasonni V (2000) Pathogenesis of Hirschsprung’s disease. J Pediatr Surg 35:1017–1025

    PubMed  CAS  Google Scholar 

  26. Hellmich HL, Kos L, Cho ES, Mahon KA, Zimmer A (1996) Embryonic expression of glial cell-line derived neurotrophic factor (GDNF) suggests multiple developmental roles in neural differentiation and epithelial-mesenchymal interactions. Mech Dev 54:95–105

    PubMed  CAS  Google Scholar 

  27. Worley DS, Pisano JM, Choi ED, Walus L, Hession CA, Cate RL, Sanicola M, Birren SJ (2000) Developmental regulation of GDNF response and receptor expression in the enteric nervous system. Development 127:4383–4393

    PubMed  CAS  Google Scholar 

  28. Young HM, Hearn CJ, Farlie PG, Canty AJ, Thomas PQ, Newgreen DF (2001) GDNF is a chemoattractant for enteric neural cells. Dev Biol 229:503–516

    PubMed  CAS  Google Scholar 

  29. Durbec P, Marcos-Gutierrez CV, Kilkenny C, Grigoriou M, Wartiowaara K, Suvanto P, Smith D, Ponder B, Costantini F, Saarma M et al (1996) GDNF signalling through the Ret receptor tyrosine kinase. Nature 381:789–793

    PubMed  CAS  Google Scholar 

  30. Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70–73

    PubMed  CAS  Google Scholar 

  31. Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ et al (1996) Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382:73–76

    PubMed  CAS  Google Scholar 

  32. Angrist M, Bolk S, Halushka M, Lapchak PA, Chakravarti A (1996) Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nat Genet 14:341–344

    PubMed  CAS  Google Scholar 

  33. Ohshiro K, Puri P (1998) Reduced glial cell line-derived neurotrophic factor level in aganglionic bowel in Hirschsprung’s disease. J Pediatr Surg 33:904–908

    PubMed  CAS  Google Scholar 

  34. Newgreen D, Young HM (2002) Enteric nervous system: development and developmental disturbances–part 2. Pediatr Dev Pathol 5:329–349

    PubMed  Google Scholar 

  35. Baynash AG, Hosoda K, Giaid A, Richardson JA, Emoto N, Hammer RE, Yanagisawa M (1994) Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 79:1277–1285

    PubMed  CAS  Google Scholar 

  36. Leibl MA, Ota T, Woodward MN, Kenny SE, Lloyd DA, Vaillant CR, Edgar DH (1999) Expression of endothelin 3 by mesenchymal cells of embryonic mouse caecum. Gut 44:246–252

    PubMed  CAS  Google Scholar 

  37. Hosoda K, Hammer RE, Richardson JA, Baynash AG, Cheung JC, Giaid A, Yanagisawa M (1994) Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell 79:1267–1276

    PubMed  CAS  Google Scholar 

  38. Bidaud C, Salomon R, Van Camp G, Pelet A, Attie T, Eng C, Bonduelle M, Amiel J, Nihoul-Fekete C, Willems PJ et al (1997) Endothelin-3 gene mutations in isolated and syndromic Hirschsprung disease. Eur J Hum Genet 5:247–251

    PubMed  CAS  Google Scholar 

  39. Amiel J, Attie T, Jan D, Pelet A, Edery P, Bidaud C, Lacombe D, Tam P, Simeoni J, Flori E et al (1996) Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease. Hum Mol Genet 5:355–357

    PubMed  CAS  Google Scholar 

  40. Southard-Smith EM, Kos L, Pavan WJ (1998) Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet 18:60–64

    PubMed  CAS  Google Scholar 

  41. Kuhlbrodt K, Herbarth B, Sock E, Hermans-Borgmeyer I, Wegner M (1998) Sox10, a novel transcriptional modulator in glial cells. J Neurosci 18:237–250

    PubMed  CAS  Google Scholar 

  42. Kuhlbrodt K, Schmidt C, Sock E, Pingault V, Bondurand N, Goossens M, Wegner M (1998) Functional analysis of Sox10 mutations found in human Waardenburg–Hirschsprung patients. J Biol Chem 273:23033–23038

    PubMed  CAS  Google Scholar 

  43. Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Prehu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G et al (1998) SOX10 mutations in patients with Waardenburg–Hirschsprung disease. Nat Genet 18:171–173

    PubMed  CAS  Google Scholar 

  44. Matchkov VV, Rahman A, Peng H, Nilsson H, Aalkjaer C (2004) Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries. Br J Pharmacol 142:961–972

    PubMed  CAS  Google Scholar 

  45. Hatano M, Aoki T, Dezawa M, Yusa S, Iitsuka Y, Koseki H, Taniguchi M, Tokuhisa T (1997) A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice. J Clin Invest 100:795–801

    Article  PubMed  CAS  Google Scholar 

  46. Shirasawa S, Yunker AM, Roth KA, Brown GA, Horning S, Korsmeyer SJ (1997) Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon. Nat Med 3:646–650

    PubMed  CAS  Google Scholar 

  47. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373:347–349

    PubMed  CAS  Google Scholar 

  48. Maeda H, Yamagata A, Nishikawa S, Yoshinaga K, Kobayashi S, Nishi K (1992) Requirement of c-kit for development of intestinal pacemaker system. Development 116:369–375

    PubMed  CAS  Google Scholar 

  49. Hagger R, Finlayson C, Kahn F, De Oliveira R, Chimelli L, Kumar D (2000) A deficiency of interstitial cells of Cajal in Chagasic megacolon. J Auton Nerv Syst 80:108–111

    PubMed  CAS  Google Scholar 

  50. Kenny SE, Connell MG, Rintala RJ, Vaillant C, Edgar DH, Lloyd DA (1998) Abnormal colonic interstitial cells of Cajal in children with anorectal malformations. J Pediatr Surg 33:130–132

    PubMed  CAS  Google Scholar 

  51. Rolle U, Piotrowska AP, Nemeth L, Puri P (2002) Altered distribution of interstitial cells of Cajal in Hirschsprung disease. Arch Pathol Lab Med 126:928–933

    PubMed  Google Scholar 

  52. Kunze WA, Furness JB (1999) The enteric nervous system and regulation of intestinal motility. Annu Rev Physiol 61:117–142

    PubMed  CAS  Google Scholar 

  53. Karaosmanoglu T, Aygun B, Wade PR, Gershon MD (1996) Regional differences in the number of neurons in the myenteric plexus of the guinea pig small intestine and colon: an evaluation of markers used to count neurons. Anat Rec 244:470–480

    PubMed  CAS  Google Scholar 

  54. Schuffler MD, Bird TD, Sumi SM, Cook A (1978) A familial neuronal disease presenting as intestinal pseudoobstruction. Gastroenterol 75:889–898

    CAS  Google Scholar 

  55. Smith VV (1993) Intestinal neuronal density in childhood: a baseline for the objective assessment of hypo- and hyperganglionosis. Pediatr Pathol 13:225–237

    PubMed  CAS  Google Scholar 

  56. Ikeda K, Goto S, Nagasaki A, Taguchi T (1988) Hypogenesis of intestinal ganglion cells: a rare cause of intestinal obstruction simulating aganglionosis. Z Kinderchir 43:52–53

    PubMed  CAS  Google Scholar 

  57. Meier-Ruge W, Morger R, Rehbein F (1970) Das hypoganglionaere megakolon als begleiterkrankung bei morbus hirschsprung. Z Kinderchir 8:254–264

    Google Scholar 

  58. Gabella G (1971) Neuron size and number in the myenteric plexus of the newborn and adult rat. J Anat 109:81–95

    PubMed  CAS  Google Scholar 

  59. Gabella G (1987) The number of neurons in the small intestine of mice, guinea-pigs and sheep. Neuroscience 22:737–752

    PubMed  CAS  Google Scholar 

  60. Wester T, O’Briain DS, Puri P (1999) Notable postnatal alterations in the myenteric plexus of normal human bowel. Gut 44:666–674

    Article  PubMed  CAS  Google Scholar 

  61. Wiley W (2002) Aging and neural control of the GI tract: III. Senescent enteric nervous system: lessons from extraintestinal sites and nonmammalian species. Am J Physiol Gastrointest Liver Physiol 283:G1020–G1026

    PubMed  CAS  Google Scholar 

  62. Gomes OA, de Souza RR, Liberti EA (1997) A preliminary investigation of the effects of aging on the nerve cell number in the myenteric ganglia of the human colon. Gerontol 43:210–217

    Article  CAS  Google Scholar 

  63. Vaos GC (1989) Quantitative assessment of the stage of neuronal maturation in the developing human fetal gut–a new dimension in the pathogenesis of developmental anomalies of the myenteric plexus. J Pediatr Surg 24:920–925

    PubMed  CAS  Google Scholar 

  64. Roman V, Krecsmarik M, Bagyanszki M, Fekete E (2001) Evaluation of the total number of myenteric neurons in the developing chicken gut using cuprolinic blue histochemical staining and neurofilament immunocytochemistry. Histochem Cell Biol 116:241–246

    PubMed  CAS  Google Scholar 

  65. Santer RM (1994) Survival of the population of NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats. J Auton Nerv Syst 49:115–121

    PubMed  CAS  Google Scholar 

  66. Takahashi T, Qoubaitary A, Owyang C, Wiley JW (2000) Decreased expression of nitric oxide synthase in the colonic myenteric plexus of aged rats. Brain Res 883:15–21

    PubMed  CAS  Google Scholar 

  67. Roberts D, Gelperin D, Wiley JW (1994) Evidence for age-associated reduction in acetylcholine release and smooth muscle response in the rat colon. Am J Physiol 267: G515–G522

    PubMed  CAS  Google Scholar 

  68. Powell AR, Reddix RA (2000) Differential effects of maturation on nicotinic- and muscarinic receptor-induced ion secretion in guinea pig distal colon. Proc Soc Exp Biol Med 224:147–151

    PubMed  CAS  Google Scholar 

  69. Matini P, Mayer B, Faussone-Pellegrini MS (1997) Neurochemical differentiation of rat enteric neurons during pre- and postnatal life. Cell Tissue Res 288:11–23

    PubMed  CAS  Google Scholar 

  70. Daniel EE, Wang YF (1999) Control systems of gastrointestinal motility are immature at birth in dogs. Neurogastroenterol Motil 11:375–392

    PubMed  CAS  Google Scholar 

  71. Hagger R, Gharaie S, Finlayson C, Kumar D (1998) Regional and transmural density of interstitial cells of Cajal in human colon and rectum. Am J Physiol 275: G1309–G1316

    PubMed  CAS  Google Scholar 

  72. Kenny SE, Connell G, Woodward MN, Lloyd DA, Gosden CM, Edgar DH, Vaillant C (1999) Ontogeny of interstitial cells of Cajal in the human intestine. J Pediatr Surg 34:1241–1247

    PubMed  CAS  Google Scholar 

  73. Ward SM, Ordog T, Bayguinov JR, Horowitz B, Epperson A, Shen L, Westphal H, Sanders KM (1999) Development of interstitial cells of Cajal and pacemaking in mice lacking enteric nerves. Gastroenterol 117:584–594

    CAS  Google Scholar 

  74. Wu JJ, Rothman TP, Gershon MD (2000) Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand. J Neurosci Res 59:384–401

    PubMed  CAS  Google Scholar 

  75. Gershon MD (2000) Hirschsprung’s Disease. Harwood Academic, Amsterdam

    Google Scholar 

  76. McLain CR Jr (1963) Amniography Studies of the Gastrointestinal Motility of the Human Fetus. Am J Obstet Gynecol 86:1079–1087

    PubMed  Google Scholar 

  77. Clark DA (1977) Times of first void and first stool in 500 newborns. Pediatrics 60:457–459

    PubMed  CAS  Google Scholar 

  78. Sherry SN, Kramer I (1955) The time of passage of the first stool and first urine by the newborn infant. J Pediatr 46:158–159

    PubMed  CAS  Google Scholar 

  79. Grand RJ, Watkins JB, Torti FM (1976) Development of the human gastrointestinal tract. A review. Gastroenterol 70:790–810

    CAS  Google Scholar 

  80. Cannon RA, Cheung AT (1989) Development of methodology for recording colonic myoelectrical activity in the infant primate. Biomater Artif Cells Artif Organs 17:81–92

    PubMed  CAS  Google Scholar 

  81. Wester T, O’Briain S, Puri P (1998) Morphometric aspects of the submucous plexus in whole-mount preparations of normal human distal colon. J Pediatr Surg 33:619–622

    PubMed  CAS  Google Scholar 

  82. Brandt CT, Graham A, Tam PK (1997) Densities of nitric oxide synthesizing nerves in smooth muscles of human gut during fetal development. J Pediatr Surg 32:1314–1317

    PubMed  CAS  Google Scholar 

  83. Giaroni C, De Ponti F, Cosentino M, Lecchini S, Frigo G (1999) Plasticity in the enteric nervous system. Gastroenterol 117:1438–1458

    CAS  Google Scholar 

  84. Yunker AM, Galligan JJ (1994) Extrinsic denervation increases NADPH diaphorase staining in myenteric nerves of guinea pig ileum. Neurosci Lett 167:51–54

    PubMed  CAS  Google Scholar 

  85. Yunker AM, Galligan JJ (1998) Extrinsic denervation increases myenteric nitric oxide synthase-containing neurons and inhibitory neuromuscular transmission in guinea pig. J Auton Nerv Syst 71:148–158

    PubMed  CAS  Google Scholar 

  86. Burks T (1994) Neurotransmission and neurotransmitters. In: Johnson L (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 211–242

    Google Scholar 

  87. Kilbinger H, Wagner P (1975) Inhibition by oxotremorine of acetylcholine resting release from guinea pig-ileum longitudinal muscle strips. Naunyn Schmiedebergs Arch Pharmacol 287:47–60

    PubMed  CAS  Google Scholar 

  88. Brookes SJ (1993) Neuronal nitric oxide in the gut. J Gastroenterol Hepatol 8:590–603

    PubMed  CAS  Google Scholar 

  89. Burleigh DE (1992) Ng-nitro-l-arginine reduces nonadrenergic, noncholinergic relaxations of human gut. Gastroenterol 102:679–683

    CAS  Google Scholar 

  90. Shuttleworth CW, Murphy R, Furness JB (1991) Evidence that nitric oxide participates in non-adrenergic inhibitory transmission to intestinal muscle in the guinea-pig. Neurosci Lett 130:77–80

    PubMed  CAS  Google Scholar 

  91. Shuttleworth CW, Xue C, Ward SM, de Vente J, Sanders KM (1993) Immunohistochemical localization of 3′,5′-cyclic guanosine monophosphate in the canine proximal colon: responses to nitric oxide and electrical stimulation of enteric inhibitory neurons. Neuroscience 56:513–522

    PubMed  CAS  Google Scholar 

  92. Vanderwinden JM, Mailleux P, Schiffmann SN, Vanderhaeghen JJ, De Laet MH (1992) Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. N Engl J Med 327:511–515

    Article  PubMed  CAS  Google Scholar 

  93. Vanderwinden JM, De Laet MH, Schiffmann SN, Mailleux P, Lowenstein CJ, Snyder SH, Vanderhaeghen JJ (1993) Nitric oxide synthase distribution in the enteric nervous system of Hirschsprung’s disease. Gastroenterol 105:969–973

    CAS  Google Scholar 

  94. Kobayashi H, O’Briain DS, Puri P (1995) Immunochemical characterization of neural cell adhesion molecule (NCAM), nitric oxide synthase, and neurofilament protein expression in pyloric muscle of patients with pyloric stenosis. J Pediatr Gastroenterol Nutr 20:319–325

    PubMed  CAS  Google Scholar 

  95. Kobayashi H, O’Briain DS, Puri P (1994) Lack of expression of NADPH-diaphorase and neural cell adhesion molecule (NCAM) in colonic muscle of patients with Hirschsprung’s disease. J Pediatr Surg 29:301–304

    PubMed  CAS  Google Scholar 

  96. Bealer JF, Natuzzi ES, Buscher C, Ursell PC, Flake AW, Adzick NS, Harrison MR (1994) Nitric oxide synthase is deficient in the aganglionic colon of patients with Hirschsprung’s disease. Pediatrics 93:647–651

    PubMed  CAS  Google Scholar 

  97. Larsson LT, Shen Z, Ekblad E, Sundler F, Alm P, Andersson KE (1995) Lack of neuronal nitric oxide synthase in nerve fibers of aganglionic intestine: a clue to Hirschsprung’s disease. J Pediatr Gastroenterol Nutr 20:49–53

    PubMed  CAS  Google Scholar 

  98. Hirakawa H, Kobayashi H, O’Briain DS, Puri P (1995) Absence of NADPH-diaphorase activity in internal anal sphincter (IAS) achalasia. J Pediatr Gastroenterol Nutr 20:54–58

    PubMed  CAS  Google Scholar 

  99. Scherer-Singler U, Vincent SR, Kimura H, McGeer EG (1983) Demonstration of a unique population of neurons with NADPH-diaphorase histochemistry. J Neurosci Methods 9:229–234

    PubMed  CAS  Google Scholar 

  100. Gabella G (1969) Detection of nerve cells by a histochemical technic. Experientia 25:218–219

    PubMed  CAS  Google Scholar 

  101. Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991) Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801

    PubMed  CAS  Google Scholar 

  102. Hope BT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814

    PubMed  CAS  Google Scholar 

  103. Furness JB, Costa M (1974) The adrenergic innervation of the gastrointestinal tract. Ergeb Physiol 69:2–51

    PubMed  CAS  Google Scholar 

  104. Ormsbee HS 3rd, Fondacaro JD (1985) Action of serotonin on the gastrointestinal tract. Proc Soc Exp Biol Med 178:333–338

    PubMed  CAS  Google Scholar 

  105. Brookes SJ (2001) Classes of enteric nerve cells in the guinea-pig small intestine. Anat Rec 262:58–70

    PubMed  CAS  Google Scholar 

  106. Holzer P (2002) Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal pain. Neurogastroenterol Motil 14:459–475

    PubMed  CAS  Google Scholar 

  107. Furness JB (2000) Types of neurons in the enteric nervous system. J Auton Nerv Syst 81:87–96

    PubMed  CAS  Google Scholar 

  108. Kirkup AJ, Brunsden AM, Grundy D (2001) Receptors and transmission in the brain-gut axis: potential for novel therapies. I. Receptors on visceral afferents. Am J Physiol Gastrointest Liver Physiol 280:G787–G794

    PubMed  CAS  Google Scholar 

  109. Furness JB, Clerc N, Gola M, Kunze WA, FletcherEK (2000) Identification of component neurons and organisations of enteric circuits. In: Krammer HJ (eds) Falk symposium 112. Nuerogastroenterology. From basic to the clinics. Kluwer, Dordrecht

  110. Porter AJ, Wattchow DA, Brookes SJ, Costa M (2002) Cholinergic and nitrergic interneurones in the myenteric plexus of the human colon. Gut 51:70–75

    PubMed  CAS  Google Scholar 

  111. Wood JD, Alpers DH, Andrews PL (1999) Fundamentals of neurogastroenterology. Gut 45(Suppl 2):II6–II16

    Article  PubMed  Google Scholar 

  112. Hansen MB (2002) Small intestinal manometry. Physiol Res 51:541–556

    PubMed  CAS  Google Scholar 

  113. Hansen MB, Dresner LS, Wait RB (1998) Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease. Physiol Res 47:307–327

    PubMed  CAS  Google Scholar 

  114. Vanden Berghe P, Bisschops R, Tack J (2001) Imaging of neuronal activity in the gut. Curr Opin Pharmacol 1:563–567

    PubMed  CAS  Google Scholar 

  115. Loening-Baucke V (1998) Constipation in children. N Engl J Med 339:1155–1156

    PubMed  CAS  Google Scholar 

  116. Loening-Baucke V (1993) Chronic constipation in children. Gastroenterol 105:1557–1564

    CAS  Google Scholar 

  117. Taitz LS, Wales JK, Urwin OM, Molnar D (1986) Factors associated with outcome in management of defecation disorders. Arch Dis Child 61:472–477

    PubMed  CAS  Google Scholar 

  118. Tomita R, Munakata K, Howard ER, Fujisaki S (2004) Histological studies on Hirschsprung’s disease and its allied disorders in childhood. Hepatogastroenterol 51:1042–1044

    Google Scholar 

  119. van Ginkel R, Reitsma JB, Buller HA, van Wijk MP, Taminiau JA, Benninga MA (2003) Childhood constipation: longitudinal follow-up beyond puberty. Gastroenterol 125:357–363

    Google Scholar 

  120. Procter E, Loader P (2003) A 6-year follow-up study of chronic constipation and soiling in a specialist paediatric service. Child Care Health Dev 29:103–109

    PubMed  CAS  Google Scholar 

  121. Holschneider AM, Meier-Ruge W, Ure BM (1994) Hirschsprung’s disease and allied disorders–a review. Eur J Pediatr Surg 4:260–266

    Article  PubMed  CAS  Google Scholar 

  122. Qualman SJ, Murray R (1994) Aganglionosis and related disorders. Hum Pathol 25:1141–1149

    PubMed  CAS  Google Scholar 

  123. Gershon MD (1981) The enteric nervous system. Annu Rev Neurosci 4:227–272

    PubMed  CAS  Google Scholar 

  124. Spouge D, Baird PA (1985) Hirschsprung disease in a large birth cohort. Teratology 32:171–177

    PubMed  CAS  Google Scholar 

  125. Puri P (1996) Hirschsprung’s disease. In: Puri P (ed) Newborn surgery. Butterworth, Oxford, pp 363–378

    Google Scholar 

  126. Cass D (1990) Aganglionosis: associated anomalies. J Paediatr Child Health 26:351–354

    PubMed  CAS  Google Scholar 

  127. Passarge E (1967) The genetics of Hirschsprung’s disease. Evidence for heterogeneous etiology and a study of sixty-three families. N Engl J Med 276:138–143

    Article  PubMed  CAS  Google Scholar 

  128. Goldberg EL (1984) An epidemiological study of Hirschsprung’s disease. Int J Epidemiol 13:479–485

    PubMed  CAS  Google Scholar 

  129. Orr JD, Scobie WG (1983) Presentation and incidence of Hirschsprung’s disease. Br Med J (Clin Res Ed) 287:1671

    Article  CAS  Google Scholar 

  130. Amiel J, Lyonnet S (2001) Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38:729–739

    PubMed  CAS  Google Scholar 

  131. Puri P (2003) Hirschsprung’s disease. In: Puri P (ed) Newborn surgery. Arnold, London

    Google Scholar 

  132. Cass DT (2000) Hirschsprung’s Disease. Harwood Academic, Amsterdam

    Google Scholar 

  133. Badner JA, Chakravarti A (1990) Waardenburg syndrome and Hirschsprung disease: evidence for pleiotropic effects of a single dominant gene. Am J Med Genet 35:100–104

    PubMed  CAS  Google Scholar 

  134. Bernfield M, Banerje S, Koda J (1984) Remodelling of basement membrane as a mechanism of morphogenetic tissue interaction. In: Trelstadt R (ed) The role of extracellular matrix in development. Alan RL Liss, New York

    Google Scholar 

  135. Brauer PR, Markwald RR (1987) Attachment of neural crest cells to endogenous extracellular matrices. Anat Rec 219:275–285

    PubMed  CAS  Google Scholar 

  136. E Okamoto TU (1967) Embryogenesis of intramural ganglia of the gut and its relation to Hirschsprung’s disease. J Pediatr Surg 2:437–443

    Google Scholar 

  137. Puri P (2000) Hirschsprung’s disease: clinical generalities. In: Puri P, Holschneider AM (eds) Hirschsprung’s disease and allied disorders. Harwood Academic, Amsterdam, pp 129–135

  138. Badner JA, Sieber WK, Garver KL, Chakravarti A (1990) A genetic study of Hirschsprung disease. Am J Hum Genet 46:568–580

    PubMed  CAS  Google Scholar 

  139. Meier-Ruge W (1971) Uber ein erkrankungsblid des colon mit hisrschsprung symptomatik. Verh Dtsch Ges Pathol 55:506–510

    PubMed  CAS  Google Scholar 

  140. Fadda B, WM Meier-Ruge W (1983) Neuronale intestinale dysplasie. Eine kritische 2-Jahresanalyse klinischer und bioptischer diagnose. Z Kinderchir 138:284–287

    Google Scholar 

  141. Puri P, Rolle U (2004) Variant Hirschsprung’s disease. Semin Pediatr Surg 13:293–299

    PubMed  Google Scholar 

  142. Puri P (2003) Intestinal neuronal dysplasia. Semin Pediatr Surg 12:259–264

    PubMed  Google Scholar 

  143. Puri P (2000) Intestinal neuronal dysplasia. In: Holschneider A, Puri P (eds) Hirschsprung’s disease and allied disorders. Harwood academic publishers, Amsterdam, pp 147–152

  144. Koletzko S, Ballauff A, Hadziselimovic F, Enck P (1993) Is histological diagnosis of neuronal intestinal dysplasia related to clinical and manometric findings in constipated children? Results of a pilot study. J Pediatr Gastroenterol Nutr 17:59–65

    PubMed  CAS  Google Scholar 

  145. Puri P (1997) Variant Hirschsprung’s disease. J Pediatr Surg 32:149–157

    PubMed  CAS  Google Scholar 

  146. Meier-Ruge W (1992) Epidemiology of congenital innervation defects of the distal colon. Virchows Arch A Pathol Anat Histopathol 420:171–177

    PubMed  CAS  Google Scholar 

  147. Milla PJ, Smith VV (1993) Intestinal neuronal dysplasia. J Pediatr Gastroenterol Nutr 17:356–357

    Article  PubMed  CAS  Google Scholar 

  148. Martucciello G, Caffarena PE, Lerone M, Mattioli G, Barabino A, Bisio G, Jasonni V (1994) Neuronal intestinal dysplasia: clinical experience in Italian patients. Eur J Pediatr Surg 4:287–292

    PubMed  CAS  Google Scholar 

  149. Csury L, Pena A (1995) Intestinal neuronal dysplasia: myth or reality? Pediatr Surg Int 10:441–446

    Google Scholar 

  150. Kapur RP (2003) Neuronal dysplasia: a controversial pathological correlate of intestinal pseudo-obstruction. Am J Med Genet A 122:287–293

    PubMed  Google Scholar 

  151. Lake BD (1995) Intestinal neuronal dysplasia. Why does it only occur in parts of Europe? Virchows Arch 426:537–539

    PubMed  CAS  Google Scholar 

  152. Oguzkurt P, Senocak ME, Akcoren Z, Buyukpamukcu N (2000) Diagnostic difficulties in neuronal intestinal dysplasia and segmental colitis. J Pediatr Surg 35:519–521

    PubMed  CAS  Google Scholar 

  153. Yamataka A, Hatano M, Kobayashi H, Wang K, Miyahara K, Sueyoshi N, Miyano T (2001) Intestinal neuronal dysplasia-like pathology in Ncx/Hox11L.1 gene-deficient mice. J Pediatr Surg 36:1293–1296

    PubMed  CAS  Google Scholar 

  154. Costa M, Fava M, Seri M, Cusano R, Sancandi M, Forabosco P, Lerone M, Martucciello G, Romeo G, Ceccherini I (2000) Evaluation of the HOX11L1 gene as a candidate for congenital disorders of intestinal innervation. J Med Genet 37:E9

    PubMed  CAS  Google Scholar 

  155. Scharli AF, Sossai R (1998) Hypoganglionosis. Semin Pediatr Surg 7:187–191

    PubMed  CAS  Google Scholar 

  156. Watanabe Y, Ito F, Ando H, Seo T, Kaneko K, Harada T, Iino S (1999) Morphological investigation of the enteric nervous system in Hirschsprung’s disease and hypoganglionosis using whole-mount colon preparation. J Pediatr Surg 34:445–449

    PubMed  CAS  Google Scholar 

  157. Rolle U, Yoneda A, Solari V, Nemeth L, Puri P (2002) Abnormalities of C-Kit-positive cellular network in isolated hypoganglionosis. J Pediatr Surg 37:709–714

    PubMed  Google Scholar 

  158. Kobayashi H, Li Z, Yamataka A, Lane GJ, Miyano T (2003) Overexpression of neural cell adhesion molecule (NCAM) antigens on intestinal smooth muscles in hypoganglionosis: is hypoganglionosis a disorder of the neuromuscular junction? Pediatr Surg Int 19:190–193

    PubMed  Google Scholar 

  159. Lake BD, Puri P, Nixon HH, Claireaux AE (1978) Hirschsprung’s disease: an appraisal of histochemically demonstrated acetylcholinesterase activity in suction rectal biopsy specimens as an aid to diagnosis. Arch Pathol Lab Med 102:244–247

    PubMed  CAS  Google Scholar 

  160. Davidson M, Bauer CH (1958) Studies of distal colonic motility in children. IV. Achalasia of the distal rectal segment despite presence of ganglia in the myenteric plexuses of this area. Pediatrics 21:746–761

    PubMed  CAS  Google Scholar 

  161. Neilson IR, Yazbeck S (1990) Ultrashort Hirschsprung’s disease: myth or reality. J Pediatr Surg 25:1135–1138

    PubMed  CAS  Google Scholar 

  162. Holschneider AM (2000) Anal sphincter achalasia and ultrashort Hirschsprung’s disease. In: Holschneider AM, Puri P (eds) Hirschsprung’s disease and allied disorders. Harwood Academic, Amsterdam, pp 399–424

    Google Scholar 

  163. Oue T, Puri P (1999) Altered intramuscular innervation and synapse formation in internal sphincter achalasia. Pediatr Surg Int 15:192–194

    PubMed  CAS  Google Scholar 

  164. Kobayashi H, Hirakawa H, Puri P (1996) Abnormal internal anal sphincter innervation in patients with Hirschsprung’s disease and allied disorders. J Pediatr Surg 31:794–799

    PubMed  CAS  Google Scholar 

  165. Piotrowska AP, Rolle U, Chertin B, De Caluwe D, Bianchi A, Puri P (2003) Alterations in smooth muscle contractile and cytoskeleton proteins and interstitial cells of Cajal in megacystis microcolon intestinal hypoperistalsis syndrome. J Pediatr Surg 38:749–755

    PubMed  Google Scholar 

  166. De Caluwe D, Yoneda A, Akl U, Puri P (2001) Internal anal sphincter achalasia: outcome after internal sphincter myectomy. J Pediatr Surg 36:736–738

    PubMed  Google Scholar 

  167. Ciamarra P, Nurko S, Barksdale E, Fishman S, Di Lorenzo C (2003) Internal anal sphincter achalasia in children: clinical characteristics and treatment with Clostridium botulinum toxin. J Pediatr Gastroenterol Nutr 37:315–319

    PubMed  CAS  Google Scholar 

  168. Langer JC, Birnbaum E (1997) Preliminary experience with intrasphincteric botulinum toxin for persistent constipation after pull-through for Hirschsprung’s disease. J Pediatr Surg 32:1059–1061; discussion 1061–1052

    Google Scholar 

  169. Puri P, Lake BD, Gorman F, O’Donnell B, Nixon HH (1983) Megacystis-microcolon-intestinal hypoperistalsis syndrome: a visceral myopathy. J Pediatr Surg 18:64–69

    PubMed  CAS  Google Scholar 

  170. Ciftci AO, Cook RC, van Velzen D (1996) Megacystis microcolon intestinal hypoperistalsis syndrome: evidence of a primary myocellular defect of contractile fiber synthesis. J Pediatr Surg 31:1706–1711

    PubMed  CAS  Google Scholar 

  171. Rolle U, O’Briain S, Pearl RH, Puri P (2002) Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy. Pediatr Surg Int 18:2–5

    PubMed  Google Scholar 

  172. Xu W, Gelber S, Orr-Urtreger A, Armstrong D, Lewis RA, Ou CN, Patrick J, Role L, De Biasi M, Beaudet AL (1999) Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci USA 96:5746–5751

    PubMed  CAS  Google Scholar 

  173. Xu W, Orr-Urtreger A, Nigro F, Gelber S, Sutcliffe CB, Armstrong D, Patrick JW, Role LW, Beaudet AL, De Biasi M (1999) Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors. J Neurosci 19:9298–9305

    PubMed  CAS  Google Scholar 

  174. Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT, Lindstrom J, Wonnacott S, Thomas GA, Smith V (2001) Megacystis-microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3 nicotinic acetylcholine receptor subunit. Gastroenterol 121:350–357

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Children’s Research Centre, Our Lady’s Children’s Hospital, University College Dublin, Crumlin, Dublin 12, Ireland

    Thambipillai Sri Paran, Udo Rolle & Prem Puri

  2. Department of Paediatric Surgery, University of Leipzig, Leipzig, Germany

    Udo Rolle

Authors
  1. Thambipillai Sri Paran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Udo Rolle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Prem Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Prem Puri.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paran, T.S., Rolle, U. & Puri, P. Enteric nervous system and developmental abnormalities in childhood. Pediatr Surg Int 22, 945–959 (2006). https://doi.org/10.1007/s00383-006-1782-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00383-006-1782-9

Keywords

Search

Navigation