• Guo Nan Yin, Woo Jean Kim, Hai-Rong Jin, Mi-Hye Kwon, Kang-Moon Song, Min Ji Choi, Jin-Mi Park, Nando Dulal Das, Ki-Dong Kwon, Dulguun Batbold, Kyu-Won Kim, Ji-Kan Ryu, and Jun-Kyu Suh.
• Department of Urology, National Research Center for Sexual Medicine, Inha University School of Medicine, Incheon, Korea.
• J Sex Med. 2013 Jun 1; 10 (6): 1488-501.

IntroductionRadical prostatectomy for prostate cancer can not only induce cavernous nerve injury (CNI) but also result in structural changes in the cavernous tissues. Nerve injury-induced protein 1, Ninjurin-1 (Ninj1), is known to be involved in neuroinflammatory processes and to be related to vascular regression during the embryonic period.AimThe study aims to determine whether and how Ninj1 neutralizing antibody (Ninj1-Ab) restores erectile function in mice with CNI.MethodsTwelve-week-old C57BL/6J mice were used and distributed into four groups: sham operation group and CNI groups receiving a single intracavernous injection of immunoglobulin G (IgG) control antibody, low-dose Ninj1-Ab (1.0 μg/20 μL), or high-dose Ninj1-Ab (2.5 μg/20 μL).Main Outcome MeasuresOne week after bilateral cavernous nerve crush, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis.ResultsThe cavernous expression of Ninj1 protein was upregulated up to 7 days after CNI and returned to baseline levels thereafter. Local delivery of Ninj1-Ab significantly increased penile neuronal nitric oxide synthase and neurofilament contents, induced cavernous endothelial proliferation and phosphorylation of Akt and endothelial nitric oxide synthase, and decreased endothelial cell apoptosis in the CNI mice by upregulating angiopoietin-1 and downregulating angiopoietin-2. High-dose Ninj1-Ab induced profound restoration of erectile function in the CNI mice (91% of sham control values), whereas low-dose Ninj1-Ab elicited partial improvement.ConclusionThe dual neurotrophic and angiogenic effects of Ninj1 blockade may provide a good opportunity for treating erectile dysfunction resulting from radical prostatectomy.© 2013 International Society for Sexual Medicine.

51 keywords...

hide…