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

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). 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. 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. 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.