PMID- 27391207 OWN - NLM STAT- MEDLINE DCOM- 20170607 LR - 20191210 IS - 1520-6777 (Electronic) IS - 0733-2467 (Linking) VI - 36 IP - 4 DP - 2017 Apr TI - 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. PG - 1046-1051 LID - 10.1002/nau.23067 [doi] AB - AIMS: 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. CONCLUSION: 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. (c) 2016 Wiley Periodicals, Inc. CI - (c) 2016 Wiley Periodicals, Inc. FAU - Wang, Zhaoxia AU - Wang Z AD - Department of Urology, China Rehabilitation Research Centre, Rehabilitation School of Capital Medical University (CMU), Beijing, China. AD - Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China. AD - Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China. FAU - Liao, Limin AU - Liao L AD - Department of Urology, China Rehabilitation Research Centre, Rehabilitation School of Capital Medical University (CMU), Beijing, China. AD - Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China. AD - Beijing Key Laboratory of Neural Injury and Rehabilitation, Beijing, China. LA - eng PT - Evaluation Study PT - Journal Article DEP - 20160708 PL - United States TA - Neurourol Urodyn JT - Neurourology and urodynamics JID - 8303326 RN - EC 2.6.1.- (Transaminases) RN - EC 2.6.1.7 (kynurenine-oxoglutarate transaminase) SB - IM MH - Animals MH - Disease Models, Animal MH - Female MH - *Gene Transfer Techniques MH - *Genetic Vectors MH - Injections MH - Pressure MH - Rats MH - Rats, Sprague-Dawley MH - *Simplexvirus MH - Transaminases/*administration & dosage MH - *Urethra/physiopathology MH - Urinary Bladder MH - Urinary Bladder, Neurogenic/etiology/therapy MH - Urination Disorders/etiology/*therapy MH - Urodynamics OTO - NOTNLM OT - KAT II OT - NMDAr OT - detrusor overactivity OT - detrusor-sphincter dyssynergia OT - gene therapy OT - herpes simple virus OT - spinal cord injury EDAT- 2016/07/09 06:00 MHDA- 2017/06/08 06:00 CRDT- 2016/07/09 06:00 PHST- 2016/04/18 00:00 [received] PHST- 2016/06/22 00:00 [accepted] PHST- 2016/07/09 06:00 [pubmed] PHST- 2017/06/08 06:00 [medline] PHST- 2016/07/09 06:00 [entrez] AID - 10.1002/nau.23067 [doi] PST - ppublish SO - Neurourol Urodyn. 2017 Apr;36(4):1046-1051. doi: 10.1002/nau.23067. Epub 2016 Jul 8.