title: GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 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.
  
  
  METHODS
  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 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.
  
  
  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.
authors: Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors: Arthur L
authors: AL
authors: Burnett
authors: Sena F
authors: SF
authors: Sezen
authors: Ahmet
authors: A
authors: Hoke
authors: Anthony O
authors: AO
authors: Caggiano
authors: Jennifer
authors: J
authors: Iaci
authors: Gwen
authors: G
authors: Lagoda
authors: Biljana
authors: B
authors: Musicki
authors: Anthony J
authors: AJ
authors: Bella
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D007001:Hypogastric Plexus / Q000378:metabolism; D008297:Male; D020890:Neuregulin-1 / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation*; D059348:Peripheral Nerve Injuries / Q000150:complications*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat
keywords: Major Pelvic Ganglia; Penis; Radical Prostatectomy; Schwann Cells; Unmyelinated Axons
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