MP1-17 THERAPEUTIC EFFECTS OF INTRAVESICAL APPLICATION OF LIPOSOME CONJUGATED WITH ANTISENSE OLIGONUCLEOTIDE TARGETING NERVE GROWTH FACTOR ON NEUROGENIC DETRUSOR OVERACTIVITY IN RATS WITH SPINAL CORD INJURY

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 2014MP1-17 THERAPEUTIC EFFECTS OF INTRAVESICAL APPLICATION OF LIPOSOME CONJUGATED WITH ANTISENSE OLIGONUCLEOTIDE TARGETING NERVE GROWTH FACTOR ON NEUROGENIC DETRUSOR OVERACTIVITY IN RATS WITH SPINAL CORD INJURY Tsuyoshi Yoshizawa, Pradeep Tyagi, Michael B. Chancellor, Satoru Takahashi, and Naoki Yoshimura Tsuyoshi YoshizawaTsuyoshi Yoshizawa More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Michael B. ChancellorMichael B. Chancellor More articles by this author , Satoru TakahashiSatoru Takahashi More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.115AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We recently reported that instillation of liposome conjugated with antisense oligonucleotide (OND) targeting nerve growth factor (NGF) into the bladder suppressed bladder overactivity in a rat model of acute cystitis (Kashyap et al., J Urol, 2013). Therefore, this study investigated whether instillation of liposome with NGF-targeting antisense OND into the bladder can suppress neurogenic detrusor overactivity shown by non-voiding contractions (NVCs) during the storage phase in rats with spinal cord injury (SCI). METHODS Adult female Sprague-Dawley rats were used. SCI was produced by complete transection of the Th8-9 spinal cord. After 3 weeks, SCI rats were divided into three groups; (a) Control group (no treatment), (b) Liposome without antisense OND group, (c) Liposome with NGF-targeting antisense OND group, in which. NGF antisense-liposome solution (1 ml) containing 6μl of anti-NGF oligonucleotide (2mM) in 994μl of liposome (7mM) was injected into the bladder and retained for 30 min. At 4 weeks after SCI, awake cystometry was performed during continuous infusion of saline (0.08 ml/min) into the bladder. Cystometric parameters evaluated included the amplitude (cmH2O) and frequency (number/min) of NVCs, maximal voiding pressure (MVP) and residual urine volume (RV). RESULTS There was no any significance in the amplitude and frequency of NVCs between control (no treatment) and liposome without antisense OND groups of SCI rats. However, in the liposome with NGF-targeting antisense OND group, the amplitude and frequency of NVCs were significantly reduced compared to control (no treatment) (38 and 55% reductions, respectively) and liposome without antisense OND groups (35 and 58% reductions, respectively) of SCI rats. MVP and RV were also significantly reduced in the NGF-targeting antisense OND group compared to other groups. CONCLUSIONS These results indicate that intravesical treatment with liposome conjugated with antisense OND targeting NGF effectively reduces neurogenic detrusor overactivity as evidenced by the reduction of NVCs in SCI rats. Because NGF upregulation in the bladder is shown to be one of the key mechanisms inducing bladder overactivity, the intravesical liposome-NGF antisense delivery could be a novel option for the treatment of neurogenic detrusor overactivity in SCI. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e7-e8 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Tsuyoshi Yoshizawa More articles by this author Pradeep Tyagi More articles by this author Michael B. Chancellor More articles by this author Satoru Takahashi More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...