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Thomas M. Fandel, Anthony J. Bella, Guiting Lin, Kavirach Tantiwongse, Ching‐Shwun Lin, Jens Pohl, Tom F. Lue, Intracavernous Growth Differentiation Factor‐5 Therapy Enhances the Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury, The Journal of Sexual Medicine, Volume 5, Issue 8, August 2008, Pages 1866–1875, https://doi.org/10.1111/j.1743-6109.2008.00881.x
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ABSTRACT
Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed.
To determine the effect of growth differentiation factor‐5 (GDF‐5) on erectile function and its mechanism in a rat model of cavernous nerve (CN) injury.
Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissues were examined by real‐time polymerase chain reaction (PCR) and immunohistochemical analyses.
Forty‐eight male Sprague‐Dawley rats were randomly divided into six equal groups: one group underwent sham operation (uninjured controls), while five groups underwent bilateral CN crush. Crush‐injury groups were treated at the time of injury with intracavernous injection of a slow‐release suspension of liquid microparticles containing no GDF‐5 (vehicle), 0.4 µg (low concentration), 2 µg (intermediate concentration), or 10 µg GDF‐5 (high concentration). One untreated group served as injured controls.
GDF‐5 enhanced erectile recovery and significantly increased intracavernous pressure in the low and intermediate‐concentration groups vs. injured controls. Low‐concentration GDF‐5 demonstrated the best functional preservation, as the intracavernous pressure increase in this group did not differ significantly from uninjured controls. A dose‐response relationship was confirmed for the effects of GDF‐5 in penile tissue. Low‐concentration GDF‐5 showed better preservation of the penile dorsal nerves and antiapoptotic effects in the corpus cavernosum (P < 0.05 vs. injured controls). Although high concentration GDF‐5 did not confer meaningful erectile recovery, this dose was more effective at decreasing transforming growth factor‐β than low‐concentration GDF‐5.
Intracavernous injection of low (0.4 µg) or intermediate‐concentration GDF‐5 (2 µg) was effective in preserving erectile function in a rat model of neurogenic erectile dysfunction. The underlying mechanism appears to involve neuron preservation and antiapoptosis.
