title: Improvement in detrusor-sphincter dyssynergia by bladder-wall injection of replication-defective herpes simplex virus vector-mediated gene delivery of kynurenine aminotransferase II in spinal cord injury rats.
abstract: METHODS
  An experimental study.
  
  
  OBJECTIVE
  To investigate the effect of replication-defective herpes simplex virus (HSV) vectors encoding the kynurenine aminotransferase II (HSVrd-KATII) gene on detrusor-sphincter dyssynergia (DSD) in spinal cord injury (SCI) rats.
  
  
  METHODS
  Beijing, China.
  
  
  METHODS
  Sprague-Dawley rats (240-265 g) were spinalized with complete transaction at the T10 level of the spinal cord. The rats were randomly divided into the following three groups: sham group (n=12, with normal saline); HSVrd group (n=12, with HSVrd) and HSVrd-KATII group (n=12, with HSVrd-KATII). One week after spinalization normal saline, HSVrd or HSVrd-KATII was injected into the bladder walls of the three groups, respectively. Three weeks after virus injection, the urethral pressure profile (UPP) and continuous cystometry were performed under awake conditions and gene expression was evaluated in all of the SCI rats.
  
  
  RESULTS
  In the HSVrd-KATII group, the maximum urethral closure pressure (Pclo.max), maximum voiding pressure (MVP), and the number and amplitude of non-voiding contraction (NVCs) were significantly decreased (34.7-39.1%, 46.7-56.2% and 31.5-32.5%, respectively), along with an increase in voiding efficiency (49.1-52.1%) compared with the sham and HSVrd groups. In addition, the levels of KATII protein and mRNA were significantly increased in the L6-S1 dorsal root ganglia (DRG) and L6-S1 spinal cord segments in the HSVrd-KATII group compared with the HSVrd group.
  
  
  CONCLUSIONS
  HSVrd vector encoding the KATII gene effectively improved DSD and detrusor overactivity by bladder-wall injection, perhaps by blocking N-methyl-d-aspartate receptors in the L6-S1 dorsal root ganglion and L6-S1 spinal cord.
authors.affiliation: Department of Urology, China Rehabilitation Research Centre, Rehabilitation School of Capital Medical University, 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: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, China Rehabilitation Research Centre, Rehabilitation School of Capital Medical University, 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: L
authors.initials: L
authors.lastname: Liao
mesh_terms: D000818:Animals; D001259:Ataxia / Q000628:therapy; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000235:genetics; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000637:Transaminases / Q000008:administration & dosage* / Q000235:genetics; D014521:Urethra / Q000473:pathology; D001743:Urinary Bladder / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000235:genetics / Q000473:pathology / Q000628:therapy*
chemical_list: D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase