title: Effect of detrusor botulinum toxin a injection on urothelial dysfunction in patients with chronic spinal cord injury: a clinical and immunohistochemistry study before and after treatment.
abstract: OBJECTIVE
  The objective of this study is to investigate the changes of urothelial junction proteins, apoptosis and suburothelial inflammation after detrusor injection of botulinum toxin A (BoNT-A) in patients with spinal cord injury (SCI) and neurogenic detrusor overactivity (NDO).
  
  
  METHODS
  A total of 26 patients with chronic suprasacral SCI and NDO were enroled. The urothelium was assessed by cystoscopic biopsy at baseline, 3 and 6 months after a single treatment of 300 U BoNT-A into the detrusor. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1) and tryptase for mast cell activity were performed. Urothelial apoptosis was also evaluated. The differences in urothelial dysfunction were compared between baseline and 3 and 6 months after treatment. Bladder biopsies from patients undergoing anti-incontinence surgery served as controls.
  
  
  RESULTS
  A single 300-U BoNT-A injection into the detrusor significantly decreased detrusor pressure and increased bladder compliance at 3 and 6 months after treatment. Significantly lower E-cadherin and ZO-1 expressions and increased mast cell and apoptotic cell counts were noted in SCI bladders compared with controls (all P<0.001). Significantly greater distributions of E-cadherin (P<0.001) and ZO-1 (P=0.05) expressions were noted 3 months after BoNT-A injection. However, these changes had declined by 6 months after treatment. Activated mast cells and urothelial apoptosis showed no significant differences between baseline and 3 or 6 months.
  
  
  CONCLUSIONS
  Urothelial dysfunction and adhesive and junction protein concentrations in SCI patients' bladders recovered after BoNT-A treatment. However, this effect decreased with time. Thus, neurogenic inflammation after SCI was not adequately improved after a single BoNT-A injection.
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
authors.forename: S-F
authors.initials: SF
authors.lastname: Chen
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien, Taiwan.
authors.forename: H-C
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D019274:Botulinum Toxins, Type A / Q000494:pharmacology / Q000627:therapeutic use*; D015820:Cadherins / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications*; D013997:Time Factors; D053802:Tryptases / Q000378:metabolism; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000209:etiology*; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D009465:Neuromuscular Agents; D062826:Zonula Occludens-1 Protein; D053802:Tryptases; D019274:Botulinum Toxins, Type A
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