title: Effect of urethral wall injection of replication-defective herpes simplex virus-mediated gene transfer of kynurenine aminotransferase on urethral pressure in spinal cord-injured rats.
abstract: OBJECTIVE
  We determined whether or not replication-defective herpes simplex virus vector-mediated kynurenine aminotransferase II (HSVrd-KAT II) suppressed the tonic activity of the urethral sphincter in spinal cord-injured (SCI) rats.
  
  
  METHODS
  Thirty-six adult female Sprague-Dawley rats were used to produce a spinal cord injury model. One week after spinalization, HSVrd-KAT II was injected into the urethral wall of rats and another two groups of SCI rats were treated with saline and HSVrd as controls. Three weeks after viral injection, the urethral pressure profile (UPP), continuous cystometry, and gene expression in the L6-S1 spinal cords were evaluated in all three groups.
  
  
  RESULTS
  In the HSVrd-KAT II group, the maximum urethral closure pressure (Pclo.max) and maximum voiding pressure were significantly decreased (23.6-24.9% and 31.6-30.9%, respectively), in addition to an increase in voiding efficiency(48.8-76%), compared with the sham and HSVrd groups. The KAT II protein and mRNA levels were significantly increased in HSV-KAT II group compared with the HSVrd group.
  
  
  CONCLUSIONS
  KAT II gene therapy effectively reduced the urethral pressure, improving detrusor-sphincter dyssynergia (DSD), and detrusor overactivity (DO), probably by blocking the N-methyl-D-aspartate receptor (NMDAr) in the L6-S1 spinal cord. Neurourol. Urodynam. 36:1046-1051, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, China Rehabilitation Research Centre, Rehabilitation School of Capital Medical University (CMU), Beijing, China.|Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.|Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, China Rehabilitation Research Centre, Rehabilitation School of Capital Medical University (CMU), Beijing, China.|Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China.|Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Liao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007267:Injections; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus; D000637:Transaminases / Q000008:administration & dosage*; D014521:Urethra / Q000503:physiopathology; D001743:Urinary Bladder; D001750:Urinary Bladder, Neurogenic / Q000209:etiology / Q000628:therapy; D014555:Urination Disorders / Q000209:etiology / Q000628:therapy*; D014563:Urodynamics
chemical_list: D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase
keywords: KAT II; NMDAr; detrusor overactivity; detrusor-sphincter dyssynergia; gene therapy; herpes simple virus; spinal cord injury