You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2012721 INOSINE IMPROVES BLADDER FUNCTION IN RATS WITH SPINAL CORD INJURY Abhishek Seth, Yeun Goo Chung, Aruna Ramachandran, Duong Tu, Eric Boxer, Vivian Cristofaro, Lin Huang, Dolores Di Vizio, Maryrose Sullivan, Carlos Estrada, and Rosalyn Adam Abhishek SethAbhishek Seth Boston, MA More articles by this author , Yeun Goo ChungYeun Goo Chung Boston, MA More articles by this author , Aruna RamachandranAruna Ramachandran Boston, MA More articles by this author , Duong TuDuong Tu Boston, MA More articles by this author , Eric BoxerEric Boxer Boston, MA More articles by this author , Vivian CristofaroVivian Cristofaro West Roxbury, MA More articles by this author , Lin HuangLin Huang Boston, MA More articles by this author , Dolores Di VizioDolores Di Vizio Boston, MA More articles by this author , Maryrose SullivanMaryrose Sullivan West Roxbury, MA More articles by this author , Carlos EstradaCarlos Estrada Boston, MA More articles by this author , and Rosalyn AdamRosalyn Adam Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.806AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Anticholinergic medications are the mainstay of medical treatment for neurogenic bladder. However, their use is limited by significant side effects, such that a search for new therapeutic approaches is warranted. Inosine is a purine nucleoside and the breakdown product of adenosine, which has anti-inflammatory and antioxidant properties. Furthermore, it has been shown to induce axonal sprouting in transected corticospinal tracts of rodents, resulting in improved motor recovery following injury. However its utility for treatment of neurogenic bladder has not been explored. In this study, we test the hypothesis that administration of inosine favorably affects bladder function after spinal cord injury in a rodent model. METHODS Forty male Sprague Dawley rats were subjected to complete extradural transection at the level of the eighth thoracic vertebra (T8). The treatment group (TI, n=20) received daily intraperitoneal injection of inosine at a dose of 225mg/kg. The control group (TC, n=20) received an equal volume of saline. Voiding behavior was analyzed in both groups at 3 and 5 wk by voided stain on paper (VSOP) analysis and urodynamic parameters were determined at 6 wk using conscious unrestrained cystometry. At the end of the experiment, bladders were harvested for ex vivo contractility studies and endpoint analyses. RESULTS VSOP analysis revealed no differences in the pattern or size of the voids between TI and TC rats at either time point. However, inosine administration led to a significant reduction in detrusor overactivity, with TI rats showing 4.3 times fewer spontaneous non-voiding contractions as TC rats (p = 0.03). TI rats also had lower peak voiding pressures compared to TC rats, but this difference did not reach significance. Interestingly, no difference was detected in force generation in response to alpha, a,b-me-ATP, phenylephrine, KCl or electrical field stimulation in detrusor strips from TI and TC rats. This suggests that inosine improves voiding function in a manner distinct from altering bladder muscle contractility. Furthermore, histological analysis of bladder cross sections from TC rats revealed a lower nerve density in the serosa and atrophic nerve fascicles compared to TI rats. CONCLUSIONS Our findings provide the first demonstration that inosine can improve voiding function through reduction of bladder overactivity in a rodent model of spinal cord injury. The ready availability and favorable safety profile of inosine suggests the potential for relatively rapid translation of these findings to the clinical arena. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e296 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Abhishek Seth Boston, MA More articles by this author Yeun Goo Chung Boston, MA More articles by this author Aruna Ramachandran Boston, MA More articles by this author Duong Tu Boston, MA More articles by this author Eric Boxer Boston, MA More articles by this author Vivian Cristofaro West Roxbury, MA More articles by this author Lin Huang Boston, MA More articles by this author Dolores Di Vizio Boston, MA More articles by this author Maryrose Sullivan West Roxbury, MA More articles by this author Carlos Estrada Boston, MA More articles by this author Rosalyn Adam Boston, MA More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...