MP84-08 TUMOR NECROSIS FACTOR ALPHA IS INCREASED AFTER CAVERNOUS NERVE INJURY AND IMPAIRS REGENERATION OF NITRERGIC NEURONS AND MODULATES PENILE SMOOTH MUSCLE TONE

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP84)1 Apr 2020MP84-08 TUMOR NECROSIS FACTOR ALPHA IS INCREASED AFTER CAVERNOUS NERVE INJURY AND IMPAIRS REGENERATION OF NITRERGIC NEURONS AND MODULATES PENILE SMOOTH MUSCLE TONE Hotaka Matsui*, Nikolai A. Sopko, Jefferey D. Campbell, Xiaopu Liu, Emmanuel Weyne, Maarten Albersen, Fabio Castiglione, Johanna L. Hannan, and Bivalacqua Trinity J Hotaka Matsui*Hotaka Matsui* More articles by this author , Nikolai A. SopkoNikolai A. Sopko More articles by this author , Jefferey D. CampbellJefferey D. Campbell More articles by this author , Xiaopu LiuXiaopu Liu More articles by this author , Emmanuel WeyneEmmanuel Weyne More articles by this author , Maarten AlbersenMaarten Albersen More articles by this author , Fabio CastiglioneFabio Castiglione More articles by this author , Johanna L. HannanJohanna L. Hannan More articles by this author , and Bivalacqua Trinity JBivalacqua Trinity J More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000976.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Erectile dysfunction is induced after cavernous nerve (CN) injury by inflammation in pelvic ganglia. We examined levels of tumor necrosis factor alpha (TNFA), after bilateral CN injury (BCNI) in vivo, and effect of exogenous TNFA (eTNFA) on neurite outgrowth from major pelvic ganglion (MPG) ex vivo. Additionally, we evaluated effect of TNFA signal inhibition to penile smooth muscle tone with TNFA receptor knockout mice (TNFRKO). METHODS: 70 male rats underwent sham or BCNI. MPGs of sham rats were collected after 48 hours. BCNI groups had MPG harvested at 6 h, 12 h, 24 h, 48 h, 7 days, or 14 days after surgery. We performed qPCR to examine gene expression of TNFA and Western blot to examine protein amount of TNFA in MPGs. Immunofluorescence(IF) for TNFA was performed in MPG. For ex vivo study, MPGs were harvested from control rats and cultured in Matrigel with eTNFA (0, 10, 20, 30 ng/mL). Neurite lengths from MPGs were measured 72 h after culture. MPGs were processed for qPCR of Tyrosine hydroxylase (TH) and neuronal nitric oxidase (nNOS). IF was assessed for TH and nNOS in MPG. To examine effect of TNFA inhibition on MPG and penis after BCNI, wild type mice (WT) and TNFRKO were randomized to undergo sham or BCNI. MPGs were harvested 48 hours after surgery to examine gene expression of nNOS and TH by qPCR. Penises were used to examine smooth muscle tone to electrical field stimulation (EFS). RESULTS: TNFA’s gene/protein expression was increased in MPGs after BCNI, with peaks at 2 and 7 days, respectively. IF showed TNFA localized to perivascular areas at 48 h and neuronal cell body at 14 days after BCNI. eTNFA inhibited neurite outgrowth in a dose-dependent fashion, and impaired gene expression of nNOS in MPG (p<0.05). MPGs cultured with eTNFA showed significantly shorter neurite lengths of nNOS+ neurons than TH+ neurons (p<0.01), while this difference was not seen in controls. TNFRKO showed enhanced gene expression of nNOS compared to WT (p<0.01). Penises of WT showed enhanced smooth-muscle contraction to EFS, compared to TNFKO (p<0.01). TNFRKO had enhanced relaxation response to EFS after maximal contraction, compared to WT (p<0.01). CONCLUSIONS: TNFA was increased following BCNI and inhibited neurite outgrowth from MPGs in a dose-dependent fashion. eTNFA lowered gene and protein expression of nNOS. TNFRKO mice showed enhanced gene expression of nNOS and enhanced penile smooth muscle relaxation. These results suggest that TNFA may selectively inhibit nNOS+ neurons, and impairs penile smooth muscle tone. Source of Funding: NIH © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1267-e1267 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hotaka Matsui* More articles by this author Nikolai A. Sopko More articles by this author Jefferey D. Campbell More articles by this author Xiaopu Liu More articles by this author Emmanuel Weyne More articles by this author Maarten Albersen More articles by this author Fabio Castiglione More articles by this author Johanna L. Hannan More articles by this author Bivalacqua Trinity J More articles by this author Expand All Advertisement PDF downloadLoading ...