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Three-Dimensional Imaging of the Enteric Nervous System in Human Pediatric Colon Reveals New Features of Hirschsprung's Disease.
Eisenberg, Joshua D; Bradley, Rebecca P; Graham, Kahleb D; Ceron, Rachel H; Lemke, Amanda M; Wilkins, Benjamin J; Naji, Ali; Heuckeroth, Robert O.
Afiliação
  • Eisenberg JD; Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Bradley RP; Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
  • Graham KD; Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicin
  • Ceron RH; Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Lemke AM; Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania.
  • Wilkins BJ; Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  • Naji A; Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Heuckeroth RO; Abramson Research Center, Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: HeuckerothR@chop.edu.
Gastroenterology ; 167(3): 547-559, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38494035
ABSTRACT
BACKGROUND &

AIMS:

Hirschsprung's disease is defined by the absence of the enteric nervous system (ENS) from the distal bowel. Primary treatment is "pull-through" surgery to remove bowel that lacks ENS, with reanastomosis of "normal" bowel near the anal verge. Problems after pull-through are common, and some may be due to retained hypoganglionic bowel (ie, low ENS density). Testing this hypothesis has been difficult because counting enteric neurons in tissue sections is unreliable, even for experts. Tissue clearing and 3-dimensional imaging provide better data about ENS structure than sectioning.

METHODS:

Regions from 11 human colons and 1 ileal specimen resected during Hirschsprung's disease pull-through surgery were cleared, stained with antibodies to visualize the ENS, and imaged by confocal microscopy. Control distal colon from people with no known bowel problems were similarly cleared, stained, and imaged.

RESULTS:

Quantitative analyses of human colon, ranging from 3 days to 60 years old, suggest age-dependent changes in the myenteric plexus area, ENS ganglion area, percentage of myenteric plexus occupied by ganglia, neurons/mm2, and neuron Feret's diameter. Neuron counting using 3-dimensional images was highly reproducible. High ENS density in neonatal colon allowed reliable neuron counts using 500-µm2 × 500-µm2 regions (36-fold smaller than in adults). Hirschsprung's samples varied 8-fold in proximal margin enteric neuron density and had diverse ENS architecture in resected bowel.

CONCLUSIONS:

Tissue clearing and 3-dimensional imaging provide more reliable information about ENS structure than tissue sections. ENS structure changes during childhood. Three-dimensional ENS anatomy may provide new insight into human bowel motility disorders, including Hirschsprung's disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colo / Sistema Nervoso Entérico / Microscopia Confocal / Imageamento Tridimensional / Doença de Hirschsprung Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged / Newborn Idioma: En Revista: Gastroenterology Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colo / Sistema Nervoso Entérico / Microscopia Confocal / Imageamento Tridimensional / Doença de Hirschsprung Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male / Middle aged / Newborn Idioma: En Revista: Gastroenterology Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos