Selective neurotrophin deficiency in infantile hypertrophic pyloric stenosis

doi:10.1053/jpsu.2001.25795

Journal of Pediatric Surgery

Volume 36, Issue 8, August 2001, Pages 1280-1284

Presented at the 2000 Annual Meeting of the Section on Surgery of the American Academy of Pediatrics, Chicago, Illinois, October 28-November 1, 2000.

https://doi.org/10.1053/jpsu.2001.25795 Get rights and content

Abstract

Background/Purpose: Increasing evidence suggests that the enteric nervous system is under the control of neurotrophins. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), promote differentiation, growth, and survival of various central and peripheral nervous system neurons. The biological effects of neurotrophins are mediated by the interactions with high-affinity tyrosine kinase receptors (TrkA, TrkB, TrkC). Recently, abnormalities of intramuscular innervation have been reported in infantile hypertrophic pyloric stenosis (IHPS). To further understand the reported abnormalities in pyloric innervation in IHPS, the authors analyzed the expression of Trk receptors and the neurotrophins content in IHPS. Methods: Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients (age range, 23 to 41 days) at pyloromyotomy and from 8 age-matched controls without gastrointestinal disease at autopsy performed within 12 hours after death. Indirect immunohistochemistry was performed using ABC (Avidin Biotin peroxidase Complex) method with anti-Trk specific antibodies (A,B,C). Quantitative analysis was performed using sandwich-type ELISA for NGF, BDNF, NT-3, and NT-4/5. Results: The intensity of staining of the myenteric plexus for TrkA, TrkB, and TrkC was similar among IHPS and controls. There was a lack of TrkA-positive nerve fibers in IHPS compared with controls. The quantity of total NGF, NT-3, and BDNF in IHPS was significantly lower than in controls. Conclusions: The reduced production of neurotrophins in IHPS may be responsible for the delay in the functional and structural maturation of pyloric innervation in IHPS. The lack of TrkA-positive nerve fibers in pyloric muscle may explain the abnormal intramuscular innervation in IHPS. J Pediatr Surg 36:1280-1284. Copyright © 2001 by W.B. Saunders Company.

Section snippets

Tissue specimens

Full-thickness pyloric muscle biopsy specimens were obtained at the time of pyloromyotomy from 8 patients with IHPS (age range, 23 to 41 days; mean, 34.5 days). Age-matched controls (age range, 14 days to 82 days; mean, 43.5 days) were taken at autopsy from patients who died without evidence of gastrointestinal disease. Autopsy was performed within 12 hours of death, and no autolysis was observed in the tissues. Controls were born at term, and the causes of death included sudden infant death

Enzyme-linked immunosorbent assay analysis

IHPS samples contained less neurotrophins than controls (Fig 1).

. Enzyme-Linked Immunosorbent Assay Analysis (ELISA): Statistically significant reduced content of NGF, BDNF, NT-3 in infantile hypertrophic pyloric stenosis.

The level of NGF in the muscle of IHPS was 2.09 ± 0.78 pg/ng of total soluble protein (mean ± SD), whereas in the muscle of normal pylorus it was 5.56 ± 1.17 pg/ng of total soluble protein. The difference was statistically significant (P <.01). The amount of BDNF in IHPS was

Discussion

Neurotrophins are a family of related, target-derived neuronal growth factors that support neuronal growth, survival and differentiation.¹⁸ All members are synthesized as precursor polypeptides that, through enzymatic cleavage, yield mature homodimeric neurotrophins. Neurotrophic interaction with target neuron receptors results in a variety of trophic and tropic events. It is well established that peripheral sensory and postganglionic sympathetic neurons are under the control of neurotrophins

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Citation Excerpt :
Furthermore, Ntrk2−/− mice show deterioration of the normal architecture of the enteric nervous system [54]. Both BDNF and TrkB expression are altered in intestinal pathologies such as Hirschprung disease and infantile hypertrophic pyloric stenosis [55,56]. Thus, it is feasible that impairments resulting from a lack of TrkB in the enteric nervous system of Phox2b-Ntrk2+/− mice could lead to a deficiency in intestinal nutrient absorption and subsequent hyperphagia in the absence of body weight differences.
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^*: Address reprint requests to Prem Puri, MS, FRCS, FRCS (Ed), FACS, Director of Research, Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.

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Selective neurotrophin deficiency in infantile hypertrophic pyloric stenosis*

Abstract

Section snippets

Tissue specimens

Enzyme-linked immunosorbent assay analysis

Discussion

J Pediatr Surg

Gastroenterology

J Pediatr Surg

Curr Opin Neurobiol

Neuron

Exp Neurol

Gastroenterology

Curr Opin Cell Biol

Neurosci Lett

Cell

Neuron

Neuroscience

J Pediatr Surg

J Pediatr Surg

J Pediatr Surg