GGF2 Is Neuroprotective in a Rat Model of Cavernous Nerve Injury-Induced Erectile Dysfunction |
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| Institution: | 2. Departments of Neurology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA;3. Acorda Therapeutics, Inc, Ardsley, NY, USA;4. Departments of Surgery and Neuroscience, Division of Urology, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada;2. Department of Psychosomatic Gynaecology and Sexology, Leiden University Medical Centre, Leiden, The Netherlands;3. Department of Sexology and Psychosomatic Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;4. Department Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands;5. Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands;2. Inflammation Research Center, VIB, Ghent University, Ghent, Belgium;3. Department of Biomedical Biology, Ghent, Belgium;2. Institute for Molecular and Cell Biology (IBMC), Universidade do Porto, Porto, Portugal;3. Department of Urology, Central Hospital of S. João, Porto, Portugal;4. Requimte/Department of Chemistry & Biochemistry, Faculty of Sciences, Universidade do Porto, Porto, Portugal;5. Faculty of Nutrition and Food Sciences, Universidade do Porto, Porto, Portugal |
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| Abstract: | IntroductionErectile dysfunction is a major complication of radical prostatectomy, commonly associated with penile neuropathy. In animal models of peripheral nerve injury, glial growth factor-2 (GGF2), a member of the neuregulin family of growth factors, has neuroprotective and neurorestorative properties, but this potential has not been established after cavernous nerve (CN) injury.AimsThe effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury.MethodsAdult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15 mg/kg) or vehicle subcutaneously 24 hour pre and 24-hour post-BCNI, and once weekly for 5 weeks. Erectile function was assessed in response to electrical stimulation of the CN. CN survival was assessed by fluorogold retrograde axonal tracing in major pelvic ganglia (MPG). Unmyelinated axons in the CNs were quantitated by electron microscopy.Main Outcome MeasuresErectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI.ResultsErectile function was decreased (P < 0.05) after BCNI, and it was improved (P < 0.05) by all doses of GGF2. The number of fluorogold-labeled cells in the MPG was reduced (P < 0.05) by BCNI and was increased (P < 0.05) by GGF2 (0.5 and 5 mg/kg). The percentage of denervated Schwann cells in the BCNI group was higher (P < 0.05) than that in the sham-treated group and was decreased (P < 0.05) in the GGF2-treated (5 mg/kg) BCNI group. In the BCNI + GGF2 (5 mg/kg) group, the unmyelinated fiber histogram demonstrated a rightward shift, indicating an increased number of unmyelinated axons per Schwann cell compared with the BCNI group.ConclusionsGGF2 promotes erectile function recovery following CN injury in conjunction with preserving unmyelinated CN fibers. Our findings suggest the clinical opportunity to develop GGF2 as a neuroprotective therapy for radical prostatectomy. Burnett AL, Sezen SF, Hoke A, Caggiano AO, Iaci J, Lagoda G, Musicki B, and Bella AJ. GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction. J Sex Med 2015;12:897–905. |
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