876 CAVERNOUS NERVE REGENERATION BY SONIC HEDGEHOG

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research II1 Apr 2010876 CAVERNOUS NERVE REGENERATION BY SONIC HEDGEHOG Nicholas Angeloni, Christopher Bond, Yi Tang, Shuming Zhang, Daniel Harrington, Kevin McKenna, Samuel Stupp, and Carol Podlasek Nicholas AngeloniNicholas Angeloni Chicago, IL More articles by this author , Christopher BondChristopher Bond Chicago, IL More articles by this author , Yi TangYi Tang Chicago, IL More articles by this author , Shuming ZhangShuming Zhang Chicago, IL More articles by this author , Daniel HarringtonDaniel Harrington Houston, TX More articles by this author , Kevin McKennaKevin McKenna Chicago, IL More articles by this author , Samuel StuppSamuel Stupp Chicago, IL More articles by this author , and Carol PodlasekCarol Podlasek Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1632AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Apoptosis of penile smooth muscle (SM) caused by cavernous nerve (CN) injury/prostatectomy is a major contributing factor to erectile dysfunction (ED) development. Understanding the mechanisms that regulate CN integrity and regeneration are critical for prevention of penile apoptosis and development of novel therapeutic approaches for ED treatment. Sonic hedgehog (SHH) is a secreted protein that is abundant in pelvic ganglia neurons and Schwann cells of the CN. Schwann cells are a critical factor in promoting axon repair in the milieu of the regenerating peripheral nerve. We propose that SHH in Schwann cells of the CN is essential to maintain CN integrity, and that local SHH protein treatment of the CN at the time of injury will speed CN regeneration and prevent penile apoptosis. In this study we have used novel peptide amphiphile “noodle” nanotechnology for local SHH protein delivery to crushed CNs and examined CN regeneration and penile morphology. METHODS Sprague Dawley rats underwent bilateral CN crush and CNs were treated with SHH noodle for 4 and 6 weeks (n=7, 9). Control rats underwent bilateral CN crush and were treated with BSA/PBS noodle (n=4, 9). Intracavernosal pressure/blood pressure (ICP/BP), electron microscopy (EM), TUNEL, and semi-quantitative immunohistochemical analysis for SHH, growth associated protein 43 (GAP43) and anti-glial fibrillary acidic protein (GFAP) were performed. RESULTS SHH treatment of the CN caused a 58% improvement in ICP/BP (p-value=0.05) 6 weeks after CN injury. SHH treated CNs showed normal morphology, while demyelination and axonal degeneration were abundant in BSA/PBS treated nerves, by EM. GFAP protein increased 22% in BSA/PBS treated CNs (p-value=0.004) while GFAP was indistinguishable from non-surgery rats in the SHH group (p-value=0.1), indicating significant regeneration. Preliminary results suggest a 36% difference in the number of growth cones in SHH and BSA/PBS treated tissues, 6 weeks after injury. CONCLUSIONS These results show that SHH protein delivered by noodle nanotechnology is effective in speeding CN regeneration and has significant clinical potential to be used as a regenerative therapy for the CN in prostatectomy patients. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e343 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Angeloni Chicago, IL More articles by this author Christopher Bond Chicago, IL More articles by this author Yi Tang Chicago, IL More articles by this author Shuming Zhang Chicago, IL More articles by this author Daniel Harrington Houston, TX More articles by this author Kevin McKenna Chicago, IL More articles by this author Samuel Stupp Chicago, IL More articles by this author Carol Podlasek Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...