TY - JOUR
T1 - GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction
AU - Burnett, Arthur L.
AU - Sezen, Sena F.
AU - Hoke, Ahmet
AU - Caggiano, Anthony O.
AU - Iaci, Jennifer
AU - Lagoda, Gwen
AU - Musicki, Biljana
AU - Bella, Anthony J.
N1 - Publisher Copyright:
© 2015 International Society for Sexual Medicine.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Erectile 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. Aims: The effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury. Methods: Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15mg/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 Measures: Erectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI. Results: Erectile 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 5mg/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 (5mg/kg) BCNI group. In the BCNI+GGF2 (5mg/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. Conclusions: GGF2 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.
AB - Erectile 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. Aims: The effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury. Methods: Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15mg/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 Measures: Erectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI. Results: Erectile 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 5mg/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 (5mg/kg) BCNI group. In the BCNI+GGF2 (5mg/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. Conclusions: GGF2 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.
KW - Major Pelvic Ganglia
KW - Penis
KW - Radical Prostatectomy
KW - Schwann Cells
KW - Unmyelinated Axons
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U2 - 10.1111/jsm.12834
DO - 10.1111/jsm.12834
M3 - Article
C2 - 25639458
AN - SCOPUS:84926420046
SN - 1743-6095
VL - 12
SP - 897
EP - 905
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
IS - 4
ER -