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Colonic Dysfunction Following Acute Spinal Cord Injury: Oxidative Damage to Interstitial Cells of Cajal?
Author(s) -
White Amanda R,
Holmes Gregory M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.371.3
Subject(s) - interstitial cell of cajal , medicine , spinal cord injury , myenteric plexus , spinal cord , descending colon , pathology , constipation , enteric nervous system , interstitial cell , rectum , immunohistochemistry , psychiatry
Over 250,000 Americans are spinal cord injured with approximately 12,000 new injuries occurring annually. Colonic dysregulation is widely acknowledged as a common co‐morbidity associated with spinal cord injury (SCI). SCI‐induced colonic dysregulation is recognized as a lifelong physical and psychological challenge for SCI patients and gravely impacts quality of life. The combined actions of the enteric nervous system (ENS) and interstitial cells of Cajal (ICC) contribute to slow‐wave propagation along much of the gastrointestinal (GI) tract including the colon. Mechanisms leading to colonic dysmotility following SCI remain largely understudied and, therefore, poorly understood, however, studies focusing on colitis, aging, and slow transit constipation suggest that ICCs are dramatically reduced and may reflect a similar mechanism of dysfunction following SCI. Aim We hypothesized that acute spinal cord injury results in colonic inflammation, elevated reactive oxygen species (ROS) thereby provoking a reduction of colonic ICCs. Methods Male Wistar rats received a contusion spinal cord injury at 3 days and 1 week prior to in vivo experimentation and tissue harvest for histological evaluation. In vivo colonic contractility was measured via a Mikro‐Tip® catheter pressure transducer that was intra‐luminally inserted within the descending colon. Whole tissue colonic samples from SCI or surgical controls were processed with DHE to visualize oxidative stress. In addition, c‐Kit immunofluorescence was performed to evaluate the colonic ICC populations within the myenteric plexus of both surgical control and SCI rats. Results Similar to previous reports of anorectal dysmotility, contraction within the descending colon were reduced following acute SCI. Preliminary data collected from DHE staining suggested an increase in ROS within the myenteric plexus of the SCI colon when compared to the surgical control. Immunofluorescent c‐Kit labeling displayed well‐structured and intact ICC networks throughout the myenteric plexus and circular muscle of the sham colon. Conversely, the 3 day SCI samples displayed ICC networks that appeared structurally normal but not completely intact and by 1 week the networks were disorganized and fragmented. With increased ROS and ICC networks progressively worsening over time, this data suggests possible prolonged inflammatory damage. Conlusion In the acute (3 day) phase of experimental SCI, diminished blood flow to the visceral tissues has been associated with increased inflammatory markers and vagally‐mediated dysmotility in the upper GI tract. Our preliminary data suggests that post‐SCI inflammation and oxidative stress may be prolonged and provoke diminished colonic motility, possibly through the disruption of intrinsic ICCs generating intrinsic pacemaker activity of smooth muscle. Support or Funding Information Support: NINDS #049177