1115 WHOLE GENOME MICROARRAY OF THE MAJOR PELVIC GANGLION AFTER CAVERNOUS NERVE INJURY: NEW INSIGHTS INTO EXPRESSION PROFILES AFTER NERVE INJURY (2011)

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 20111115 WHOLE GENOME MICROARRAY OF THE MAJOR PELVIC GANGLION AFTER CAVERNOUS NERVE INJURY: NEW INSIGHTS INTO EXPRESSION PROFILES AFTER NERVE INJURY Giulia Calenda, Travis Strong, Christian Pavlovich, Arthur Burnett, Kelvin Davies, and Trinity Bivalacqua Giulia CalendaGiulia Calenda Bronx, NY More articles by this author , Travis StrongTravis Strong Baltimore, MD More articles by this author , Christian PavlovichChristian Pavlovich Baltimore, MD More articles by this author , Arthur BurnettArthur Burnett Baltimore, MD More articles by this author , Kelvin DaviesKelvin Davies Bronx, NY More articles by this author , and Trinity BivalacquaTrinity Bivalacqua Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.712AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) is an adverse quality of life outcome with prostate cancer treatment despite current modifications of radical prostatectomy which include preservation of the cavernous nerves (CN) essential for erections. The molecular mechanisms of the intrinsic ability of CN to regenerate and promote axonal outgrowth after injury has not been fully elucidated. The purpose of this study was to use genomic expression profiling to identify candidate genes involved in injury and repair of CN after crush injury. METHODS Two groups of rats were utilized: 1) sham, and 2) bilateral CN injury (BCNI). The majorpelvic ganglion (MPG) was removed 48 h and 14 days after BCNI and haematoxylin & eosin stain as well as RNA were isolated. Agilent 44K whole rat genome microarray was performed to evaluate MPG genomic changes after CN injury at both time points and compared to sham. Expression analysis was performed using the Ingenuity Pathway Analysis system (p value ≤ 0.001, B ≥ 4). In vivo erectile responses to cavernous nerve stimulation (CNS) were evaluated. RESULTS Erectile responses to CNS were significantly decreased in 48 h and 14 day BCNI rats. A comparative analysis of global gene expression in the MPG showed 60 commonly changed genes, 232 genes unique to 48h, 50 genes unique to 14 days. Genomic changes were ≈80% induction of gene expression and ≈20% suppression. In addition to a sustained inflammatory and immune response, the expression of several genes with functions related to tissue differentiation, growth and proliferation was significantly changed. A strong early mobilization of repair and neuroprotection mechanisms (SERPINF1, IGF1, PLAU/PLAUR, ARG1) occurred, suggesting a rapid onset of repair process. We focused on the detection of changes in genes related to nervous tissue repair and proliferation. Genes related to nervous system development (ATF3 GJA1, PLAU, SERPINE1), nerve regeneration (SERPINE2, IGF1, ATF3, ARG1) and synaptic transmission (GJC1, GAL) were changed. In apparent contradiction several detected genes (A2M, ATF3, C3, EGR4, FN1, GJA1, GAL) were related to proliferation as well as apoptosis, possibly part of a protective mechanism. CONCLUSIONS Our results show multiple biologic processes associated with injury and repair of the CN and provide a systematic genome wide screen for neurotrophic and/or inhibitory pathways of nerve regeneration. These data identify candidate genes that may be utilized for novel molecular-based therapies for preservation and protection of the CN during radical prostatectomy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e448 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Metrics Author Information Giulia Calenda Bronx, NY More articles by this author Travis Strong Baltimore, MD More articles by this author Christian Pavlovich Baltimore, MD More articles by this author Arthur Burnett Baltimore, MD More articles by this author Kelvin Davies Bronx, NY More articles by this author Trinity Bivalacqua Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...