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Sham rats\u2019 MPGs were harvested after 48 hours, whereas BCNI groups\u2019 MPGs were at 6, 12, 24, 48 hours, 7, or 14 days after surgery. qPCR was used to evaluate gene expression of markers for neuroinflammation in MPGs. Western blot was performed to evaluate TNF-\u03b1 protein amount in MPGs. MPGs were harvested from healthy rats and cultured in Matrigel with TNF-\u03b1. Neurite outgrowth from MPGs was measured after 3 days, and TH and nNOS immunofluorescence was assessed. Wild type (WT) and TNFRKO mice were used to examine effect of TNF-\u03b1 inhibition on smooth muscle function after BCNI. MPGs were harvested 48 hours after sham or BCNI surgery to evaluate gene expression of nNOS and TH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>Gene expression of TNF-\u03b1 signaling pathway, Schwann cell and macrophage markers, protein expression of TNF-\u03b1 in MPGs, and penile smooth muscle function to electrical field stimulation (EFS) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>BCNI increased gene and protein expression of TNF-\u03b1 in MPGs. Exogenous TNF-\u03b1 inhibited MPG neurite outgrowth. MPGs cultured with TNF-\u03b1 had decreased gene expression of nNOS (P &amp;lt; .05). MPGs cultured with TNF-\u03b1 had shorter nNOS+ neurites than TH+ neurites (P &amp;lt; .01). Gene expression of nNOS was enhanced in TNFRKO mice compared to WT mice (P &amp;lt; .01). WT mice showed enhanced smooth muscle contraction of penises of WT mice was enhanced to EFS, compared to TNFKO (P &amp;lt; .01). Penile smooth-muscle relaxation to EFS was greater in TNFKO mice compared to WT (P &amp;lt; .01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Translation<\/jats:title>\n                    <jats:p>TNF-\u03b1 inhibition may prevent ED after prostatectomy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strength\/Limitations<\/jats:title>\n                    <jats:p>TNF-\u03b1 inhibition might prevent loss of nitrergic nerve apoptosis after BCNI and preserve corporal smooth muscle function but further investigation is required to evaluate protein expression of nNOS in MPGs of TNFKO mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>TNF-\u03b1 inhibited neurite outgrowth from MPGs by downregulating gene expression of nNOS and TNFRKO mice showed enhanced gene expression of nNOS and enhanced penile smooth-muscle relaxation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.jsxm.2021.05.001","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T18:12:39Z","timestamp":1626286359000},"page":"1181-1190","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Increased Level of Tumor Necrosis Factor-Alpha (TNF-\u03b1) Leads to Downregulation of Nitrergic Neurons Following Bilateral Cavernous Nerve Injury and Modulates Penile Smooth Tone"],"prefix":"10.1093","volume":"18","author":[{"given":"Hotaka","family":"Matsui","sequence":"first","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine , Baltimore, MD , USA"},{"name":"Department of Urology, The University of Tokyo , , Tokyo , Japan"},{"name":"Faculty of Life Sciences and Medicine, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai A.","family":"Sopko","sequence":"additional","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Campbell","sequence":"additional","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopu","family":"Liu","sequence":"additional","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine , Baltimore, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"School of Medicine, Duke University , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Weyne","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Urology, Department of Development and Regeneration, University of Leuven , Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Castiglione","sequence":"additional","affiliation":[{"name":"Division of Surgery and Interventional Science, University College London , London , UK"},{"name":"Division of Oncology \/ Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Albersen","sequence":"additional","affiliation":[{"name":"Laboratory for Experimental Urology, Department of Development and Regeneration, University of Leuven , Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna 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