PD36-04 TNF-α INHIBITS NEURITE OUTGROWTH FROM THE MAJOR PELVIC GANGLION BY INDUCING M1/M2 MACROPHAGES EX VIVO.

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2015PD36-04 TNF-α INHIBITS NEURITE OUTGROWTH FROM THE MAJOR PELVIC GANGLION BY INDUCING M1/M2 MACROPHAGES EX VIVO. Hotaka Matsui, Johanna L. Hannan, Xiaopu Liu, Ahmet Hoke, and Trinity J. Bivalacqua Hotaka MatsuiHotaka Matsui More articles by this author , Johanna L. HannanJohanna L. Hannan More articles by this author , Xiaopu LiuXiaopu Liu More articles by this author , Ahmet HokeAhmet Hoke More articles by this author , and Trinity J. BivalacquaTrinity J. Bivalacqua More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2253AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) is a common sequela after radical prostatectomy (RP) despite nerve-sparing surgery. Recently, we identified that tumor necrosis factor-alpha (TNF-α) is increased in major pelvic ganglion (MPG) following bilateral cavernous nerve injury (BCNI). We hypothesize that TNF-α impairs regeneration of cavernous nerve (CN) by inducing macrophages. To test this hypothesis, we examined exogenous TNF-α's effect on neurite outgrowth from MPG and gene expressions of macrophage markers ex vivo. METHODS Whole MPGs were harvested from Male Sprague-Dawley rats (300g) and cultured in Matrigel with or without TNF-α (20ng/ml). We measured neurite lengths from MPGs in each field at 48 and 72 hours after culture. Cultured MPGs were collected after 72 hours to evaluate gene expressions of TNF-α, inducible nitric oxide synthase (iNOS: M1 macrophage marker), arginase-1 (Arg1: M2 macrophage marker) by qPCR. RESULTS Average neurite lengths of MPGs cultured with exogenous TNF-α at 48 and 72 hours were significantly shorter than the control (p<0.05). In the control group, histogram of neurite lengths showed a single peak at the mean length. In the TNF-α group, histogram had two peaks: one at the mean of the control and the other at much shorter length. To demonstrate this difference quantitatively, variances of the both groups were compared. The variance of the TNF-α group was significantly larger than the control group's at 72 hours (p<0.05). MPGs incubated with TNF-α had increased gene expressions of iNOS, Arg1 and TNF-α (p<0.01). CONCLUSIONS This study demonstrates that exogenous TNF-α treatment inhibits neurite outgrowth from MPG. However, outgrowths of some neurites were not inhibited by TNF-α. Furthermore, exogenous TNF-α can induce increased expression of iNOS, Arg1 and TNF-α, suggesting that TNF-α recruits M1/M2 macrophages via positive feedback. These results imply that TNF-α inhibition may be a future therapy to prevent post-operative ED after RP. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e765-e766 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hotaka Matsui More articles by this author Johanna L. Hannan More articles by this author Xiaopu Liu More articles by this author Ahmet Hoke More articles by this author Trinity J. Bivalacqua More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...