748 REMOTE FROM INJURY-SITE DELIVERY OF GLIAL GROWTH FACTOR 2 (GGF2) FACILITATES RECOVERY OF ERECTILE DYSFUNCTION FOLLOWING BILATERAL CAVERNOUS NERVE INJURY IN THE RAT WITH DIRECT EVIDENCE OF CAVERNOUS NERVE PRESERVATION

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research1 Apr 2011748 REMOTE FROM INJURY-SITE DELIVERY OF GLIAL GROWTH FACTOR 2 (GGF2) FACILITATES RECOVERY OF ERECTILE DYSFUNCTION FOLLOWING BILATERAL CAVERNOUS NERVE INJURY IN THE RAT WITH DIRECT EVIDENCE OF CAVERNOUS NERVE PRESERVATION Anthony J. Bella, Jennifer F. Iaci, Elaine Coderre, Leo P. Renaud, and Anthony O. Caggiano Anthony J. BellaAnthony J. Bella Ottawa, Canada More articles by this author , Jennifer F. IaciJennifer F. Iaci Hawthorne, NY More articles by this author , Elaine CoderreElaine Coderre Ottawa, Canada More articles by this author , Leo P. RenaudLeo P. Renaud Ottawa, Canada More articles by this author , and Anthony O. CaggianoAnthony O. Caggiano Hawthorne, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1773AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are no treatments available for neuroprotection or regeneration of the cavernous nerves before/at/after injury occuring at radical prostatectomy. An optimal therapeutic would reduce initial injury and aid endogenous recovery through neuroprotective and neurorestorative mechanisms without incurring oncological risk. The neuregulin growth factor family consists of multiple isoforms essential for normal nervous system development and function. A full length product of the neuregulin-1 gene known as glial growth factor 2 (GGF2) previously demonstrated central nervous system neuroprotection. We present data that supports GGF2 as a peripheral nervous system neuromodulator, for which an application patent has been granted; a practical translational advantage is that GGF2 is effective with peripheral administration, allowing for remote from injury-site delivery. METHODS 3-month old Sprague-Dawley male rats (n=8 each) were treated as controls, crush only, and low and high dose GGF2 (0.5 and 5.0 mg/kg groups) 24 hrs pre crush, 24 hrs post crush and q7 day until study end. Change in intracavernous pressure (ICP) was standardized to mean arterial pressure (MAP) at 5 week electrostimulation. Retrograde axonal transport of fluorogold to the major pelvic ganglion and cavernous body was quantified. Proximal corpora were cryosectioned and stained against the catecholamine synthesis marker tyrosine hydroxylase (TH), neuronal NO synthase (nNOS), and vesicular acetylcholine transporter (VaChT). RESULTS ICP/MAP for control animals was 0.81 versus crush-control cohort of 0.16; low and high dose GGF2 demonstrated significant (p<0.05) improvement with ICP/MAP ratios of 0.40 and 0.54. Corporal flurogold injection indicated nerve fiber preservation and re-projection through the injured area. Cavernous body determination of nNOS,TH and VaChT were significantly reduced in crush injury and preserved with treatment. CONCLUSIONS This is the first study to demonstrate GGF2 neuromodulation in a model of radical prostatectomy induced CN injury as well as the first GGF2 treatment effects upon the peripheral nervous system. GGF2 confers a recovery advantage for CN function post- injury as measured by ICP/MAP and intact parasympathetic neurons. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e301 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony J. Bella Ottawa, Canada More articles by this author Jennifer F. Iaci Hawthorne, NY More articles by this author Elaine Coderre Ottawa, Canada More articles by this author Leo P. Renaud Ottawa, Canada More articles by this author Anthony O. Caggiano Hawthorne, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...