PD62-07 TUMOR NECROSIS FACTOR ALPHA (TNF- Α) INHIBITOR IMPROVED ERECTILE FUNCTION IN A BILATERAL CAVERNOUS NERVE INJURY RAT MODEL

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (PD62)1 Sep 2021PD62-07 TUMOR NECROSIS FACTOR ALPHA (TNF- Α) INHIBITOR IMPROVED ERECTILE FUNCTION IN A BILATERAL CAVERNOUS NERVE INJURY RAT MODEL James Liu, Hotaka Matsui, Kara Lombardo, Serkan Karakus, Arthur Burnett, and Trinity Bivalacqua James LiuJames Liu More articles by this author , Hotaka MatsuiHotaka Matsui More articles by this author , Kara LombardoKara Lombardo More articles by this author , Serkan KarakusSerkan Karakus More articles by this author , Arthur BurnettArthur Burnett More articles by this author , and Trinity BivalacquaTrinity Bivalacqua More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002099.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) after injury to the peripheral cavernous nerves (CN) is partially the result of an increase in neuroinflammation in the pelvic ganglia. Inflammatory cytokines have been implicated in axonal degeneration and neuropathy. This study examines the role of the inflammatory cytokine, tumor necrosis factor –alpha (TNF- α), after bilateral CN injury (BCNI) in vivo. We also investigate the effect of commercially available TNF- α inhibitors (Infliximab) on erectile function restoration in the BCNI rodent model. METHODS: Seventy male Sprague Dawley rats were randomized to undergo either BCNI or sham surgery. Sham rats major pelvic ganglion (MPG) were harvested after 48 hours, whereas the BCNI groups had MPG harvested at 6 hours, 12 hours, 24 hours, 48 hours, 7 days, or 14 days after BCNI. MPGs were analyzed by qPCR to evaluate gene expression of TNF-α, TNF- αR1, TNF- αR2 and markers of macrophages (CD11b and CD68). Western blot of MPGs were also performed to confirm these finding. Additionally, 25 Sprague Dawley rats were randomized to three groups: sham surgery, BCNI, or BCNI treated with TNF- α inhibitor (Infliximab) (5mg/kg weekly) for two weeks and then underwent cavernous nerve stimulation and erectile parameters were measured (peak ICP, ICP/MAP, and total ICP). RESULTS: BCNI significantly increased (p<0.05) gene and protein expression of TNF- α and its receptors (R1, R2) in rat MPGS, with peak levels were observed at 2 and 7 days, respectively. Corresponding macrophage markers (CD11b and CD68) were significantly increased (p<0.05) following BCNI with maximal expression at 48 hours. Erectile response studies demonstrated that rodents treated with TNF- α inhibitors had significantly improved (p<0.05) erectile function (ICP/MAP) at all voltages compared to BCNI alone (2V: 0.203 vs 0.057, 4V: 0.279 vs 0.081, 6V: 0.317 vs 0.166. Control 2V: 0.347, 4V: 0.414, 6V: 0.486). Peak ICP and total ICP were also significantly (p<0.05) improved compared to BCNI rats. CONCLUSIONS: TNF- α is a key inflammatory cytokine which contributes to neuroinflammation following BCNI. Treatment with commercially available TNF- α inhibitor results in mitigation of erectile dysfunction in a BCNI rat model when administered at the time of nerve injury. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1074-e1075 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Liu More articles by this author Hotaka Matsui More articles by this author Kara Lombardo More articles by this author Serkan Karakus More articles by this author Arthur Burnett More articles by this author Trinity Bivalacqua More articles by this author Expand All Advertisement Loading ...