Urothelial dysfunction and chronic inflammation in patients with spinal cord injuries at different levels and correlation with urodynamic findings

Neurourol Urodyn. 2015 Nov;34(8):757-62. doi: 10.1002/nau.22650. Epub 2014 Jul 25.

Abstract

Aims: To investigate urothelial dysfunction and suburothelial inflammation in patients with chronic SCI at different spinal cord levels.

Methods: Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1), tryptase (mast cell activation), and apoptosis tests on bladder biopsy specimens including urothelium and suburothelium were performed in 34 chronic SCI patients and 10 controls. Video-urodynamic studies were also analyzed and correlated with immunofluorescence findings.

Results: The mean interval from SCI to bladder biopsy was 9.3 ± 8.4 years. Patients with chronic SCI had significantly lower expression of E-cadherin (20.86 ± 14.07 vs. 42.40 ± 16.73, the fluorescence intensity per 4 µm(2)) and ZO-1 (5.54 ± 3.73 vs. 11.01 ± 5.66, the fluorescence intensity per 4 µm(2)) than controls (both P < 0.05). Additionally, suburothelial activated mast cells (16.60 ± 6.85 vs. 1.25 ± 1.15, positive cells per 100 cells) and apoptotic cell numbers (5.39 ± 4.86 vs. 0.08 ± 0.26, positive cells per 100 cells) were significantly higher than in controls (both P < 0.05). Immunofluorescence characteristics and video-urodynamic findings did not differ between patients with 15 cervical and 19 thoracic SCIs. Suburothelial activated mast cell numbers correlated negatively to E-cadherin expression in the urothelium (r = -0.559, P < 0.05). Additionally, apoptotic cell number correlated negatively with cystometric bladder capacity (r = -0.535, P < 0.05).

Conclusions: Decreased expression of urothelial adhesion and junction proteins and increased suburothelial inflammation and apoptosis were found in patients with chronic SCI, regardless of injury level. Such mechanisms might contribute to the vulnerability of patients with SCI to cystitis and recurrent bacterial infections.

Keywords: chronic spinal cord injury; suburothelial inflammation; urothelial dysfunction; video-urodynamic studies.

MeSH terms

  • Adult
  • Apoptosis / physiology
  • Cadherins / metabolism
  • Female
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Male
  • Middle Aged
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology*
  • Tryptases / metabolism
  • Urination Disorders / etiology
  • Urination Disorders / metabolism
  • Urination Disorders / physiopathology*
  • Urodynamics / physiology*
  • Urothelium / metabolism
  • Urothelium / physiopathology*
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Cadherins
  • Zonula Occludens-1 Protein
  • Tryptases