Selective neurotrophin deficiency in infantile hypertrophic pyloric stenosis.
OBJECTIVE
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.
Guarino
N
N
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Yoneda
A
A
Shima
H
H
Puri
P
P
D000704:Analysis of Variance; D001707:Biopsy, Needle; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D046508:Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis* / Q000172:deficiency*; D020933:Neurotrophin 3 / Q000032:analysis; D011336:Probability; D011707:Pyloric Stenosis / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D012016:Reference Values; D012680:Sensitivity and Specificity
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020794:Receptor Protein-Tyrosine Kinases