MP76-01 INVESTIGATION INTO CONSTITUTIVE EXPRESSION OF NERVE GROWTH FACTOR IN BLADDER BY BLADDER WALL INJECTION OF NGF ANTISENSE (2014)

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-neurogenic Voiding Dysfunction1 Apr 2014MP76-01 INVESTIGATION INTO CONSTITUTIVE EXPRESSION OF NERVE GROWTH FACTOR IN BLADDER BY BLADDER WALL INJECTION OF NGF ANTISENSE Pradeep Tyagi, Mahendra Kashyap, Michael Chancellor, and Naoki Yoshimura Pradeep TyagiPradeep Tyagi More articles by this author , Mahendra KashyapMahendra Kashyap More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2394AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Overexpression of nerve growth factor NGF in bladder has been established as a key molecular mediator in the lower urinary tract symptoms. Overactive bladder patients responding to intradetrusor injection of botulinum toxin showed a reduced NGF expression in histological specimens. In our previous study, bladder instillation of NGF antisense was able to directly suppress the inducible NGF expression in urothelium following acetic acid insult, but the effect of intravesical treatment on the detrusor expression of NGF was inconclusive. Therefore in the present study, we explored the direct effect of bladder wall injection of NGF antisense on the NGF expression in different regions of the bladder. METHODS Adult female Sprague-Dawley rats were given bladder wall injection (10-20μL) of either saline (sham) (n=3) or NGF antisense (0.1-10μM) complexed with liposomes under isoflurane anesthesia(n=6). Total volume of injection was split into four sites around the bladder. Abdomen was sutured back after surgery and animal returned to cages. 48h after injection, open transurethral cystometry under urethane anaesthesia (dose 1g/kg, subcutaneously) was performed with saline infused at 0.04ml/min. Bladder was harvested following sacrifice for measuring NGF protein levels by ELISA. RESULTS Cystometric parameters were indistinct between sham and the treated groups. The measured tissue specific NGF levels were normalized to the respective protein concentration and expressed as pg/mg of protein. There was insignificant difference in the NGF levels of two tissue regions from sham group with 295.8± 10.26pg/mg in urothelium and 273.9± 46.28pg/mg in detrusor(n=3). In contrast, bladder wall injection of NGF antisense reduced the constitutive production of NGF in both urothelium and detrusor regions. Paired analysis of NGF levels in urothelium and detrusor for the antisense treated group found significant reduction in detrusor relative to the higher levels in urothelium 262.0± 15.76pg/mg vs 286.8± 23.28pg/mg, respectively (p<0.05). CONCLUSIONS Gene silencing of NGF gene in detrusor following bladder wall injection supports the intradetrusor injection of NGF antisense complexed with liposome as a potential treatment for refractory overactive bladder associated with NGF overexpression in bladder smooth muscle. NGF antisense is able to suppress both constitutive and inducible expression of NGF in bladder, and inducible NGF expression has implications in the OAB pathophysiology. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e882 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Pradeep Tyagi More articles by this author Mahendra Kashyap More articles by this author Michael Chancellor More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...