1686 MOLECULAR EVIDENCE OF BRAIN FUNCTIONAL CHANGES FOLLOWING SURGICAL REDUCTION OF BLADDER VOLUME IN RATS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Non-Neurogenic Voiding Dysfunction II1 Apr 20101686 MOLECULAR EVIDENCE OF BRAIN FUNCTIONAL CHANGES FOLLOWING SURGICAL REDUCTION OF BLADDER VOLUME IN RATS Biji Sreedhar, Chung Kwong Yeung, Mei Diao, and Yimin Shi Biji SreedharBiji Sreedhar Hong Kong SAR, Hong Kong More articles by this author , Chung Kwong YeungChung Kwong Yeung Hong Kong SAR, Hong Kong More articles by this author , Mei DiaoMei Diao Hong Kong, Hong Kong More articles by this author , and Yimin ShiYimin Shi Hong Kong SAR, Hong Kong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1511AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Our recent study revealed that enuretic children have more light sleep associated with frequent cortical arousals suggesting an interaction between bladder overactivity and brain arousability. The neurons of the lateral hypothalamic and perifornical areas that express Hypocretin/Orexin(Hcrt/Orx) have been implicated in control of sleep- wake cycle and CNS arousal mechanisms. We therefore propose to use an animal model to evaluate brain functional changes in response to bladder dysfunction by the surgical reduction in bladder volume. METHODS 24 male New Zealand Wistar rats were randomly assigned to receive either sham (n=12) operation or surgical reduction of bladder volume (RBV, n=12). Animals were kept in metabolic cages and voided volume and voiding frequency were monitored. Radiotelemeters were implanted in both groups 4 weeks postoperatively. Telemetric electroencephalogram plus electromyogram were performed 2 weeks after implantation. Sleep architecture and cortical arousals were evaluated manually.Animals were anesthetized bladder and brain samples were harvested.To evaluate the molecular changes in detrusor smooth muscles(DSM) induced by bladder dysfunction, relative expression of mRNA transcript for isoforms of Myosin in DSM was determined using PCR analysis. Serial cryostat sections of brain were obtained throughout hypothalamus and the sections were immunostained to assess the associated changes in neural pathways in brainstem. RESULTS Our results demonstarted voiding dysfunction in RBV group (Mean voided volume: 0.95 ± 0.186 vs 1.75 ± 0.299 ml; frequency: 2.53± 0.30 vs. 0.53± 0.05/hr p<0.005; RBV vs Sham). Light non-rapid eye movement sleep occurred significantly more (59.2% vs 35.6%, p<0.005) and deep sleep occurred significantly less in RBV group (32.3% vs 52.8%; p<0.005). A significant increase in the expression of SM-A isoform was observed in DSM samples obtained from RBV group compared to sham (85±6% vs 15±4% respectively). A significant increase in Hcrt/Orx cell size was observed in RBV group compared to sham (25 ± 3μm vs 19 ± 2μm respectively). Moreover, marked increase in total number of hypothalamic cells expressing Hcrt -1 was observed in RBV group compared(76.57± 8 vs. 42 ± 4.71/section respectively,p<0.001). CONCLUSIONS Our results demostarted that bladder dysfunction induced significant impairments in central neurotransmission and induces changes in sleep architecture.The results further confirm the existence of a bi-directional dialogue between dysfunctional bladder and brain. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e651-e652 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Biji Sreedhar Hong Kong SAR, Hong Kong More articles by this author Chung Kwong Yeung Hong Kong SAR, Hong Kong More articles by this author Mei Diao Hong Kong, Hong Kong More articles by this author Yimin Shi Hong Kong SAR, Hong Kong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...