title: The enteric nervous system and the musculature of the colon are altered in patients with spina bifida and spinal cord injury.
abstract: Neurogenic bowel dysfunction occurs in a large percentage of adult patients with spina bifida (SB) and spinal cord injury (SCI), significantly affecting their quality of life. Although bowel motility is autonomously regulated by the enteric nervous system (ENS), disruption of the modulation of the ENS by extrinsic innervation as present in many patients with SB and SCI might lead to motility disorders. In order to gain insight in the pathophysiology, we studied histological changes of the neuromuscular structures in the colon of SB and SCI patients. Archival colon tissue blocks from SB (n = 13) and SCI (n = 34) patients were collected nationwide in The Netherlands and compared with control samples (n = 16). Histological (semiquantitative) evaluation of the ENS, the network of interstitial cells of Cajal (ICC), and the muscularis propria was performed using hematoxylin and eosin, periodic acid Schiff, and elastic von Gieson staining, and immunohistochemistry with antibodies against HuC/D, calretinin, S100, CD117, α-smooth muscle actin, and desmin. Compared to controls, SB and SCI patients showed neuronal loss and decreased nerve fiber density in the myenteric plexus. Lower nerve fiber density was significantly more often found in patients with severe bowel dysfunction. Other major findings were loss of ICCs around the myenteric plexus and fibrosis in the longitudinal muscle layer. Altered histology of the ENS may explain abnormal intestinal motility in SB and SCI patients. Furthermore, loss of myenteric nerve fibers (including enteric glial cells) may play a major role in the development of severe motility complaints.
authors.affiliation: Department of Pathology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Marjanne.denBraber-Ymker@radboudumc.nl.
authors.forename: Marjanne
authors.initials: M
authors.lastname: den Braber-Ymker
authors.affiliation: Department of Pathology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.|Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium.|MIPRO, University of Antwerp, Antwerp, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Lammens
authors.affiliation: Department of Clinical Neurophysiology, MIRA, Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|Department of Neurology and Clinical Neurophysiology, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Michel J A M
authors.initials: MJ
authors.lastname: van Putten
authors.affiliation: Department of Pathology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Iris D
authors.initials: ID
authors.lastname: Nagtegaal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016135:Spinal Dysraphism / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Colon; Immunohistochemistry; Intestinal motility; Neuromuscular disease; Spina bifida; Spinal cord injury