The additive erectile recovery effect of brain-derived neurotrophic factor combined with vascular endothelial growth factor in a rat model of neurogenic impotence

OBJECTIVE: To test the hypothesis that combined intracavernosal injection with vascular endothelial growth factor (VEGF) with adeno-associated virus-mediated brain-derived neurotrophic factor (AAV-BDNF) synergistically facilitates the neural regeneration and erectile function after cavernosal nerve injury. MATERIALS AND METHODS: Forty Sprague-Dawley male rats were randomly divided into five equal groups: eight had a sham operation while 32 had bilateral cavernosal nerve freezing followed by an immediate intracavernosal injection with either phosphate-buffered saline (PBS), VEGF, AAV-BDNF, or AAV-BDNF + VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and samples of the major pelvic ganglia and penile tissue were evaluated histologically. RESULTS: In this animal model of impotence from nerve injury, the recovery of erectile function was greatest in those receiving AAV-BDNF + VEGF; the mean (sd) maximal intracavernosal pressure in this group was 87.2 (20.78) cmH2O, compared with 37.3 (11.39) for VEGF alone and 49.8 (29.58) for AAV-BDNF alone. No erectile dysfunction was identified in the sham group, with a pressure of 100.7 (22.70) cmH2O, while all treatment groups significantly outperformed the PBS (control) group, at 29.3 (13.52) cmH2O. Furthermore, all animals receiving monotherapy or combined treatment had more NADPH-diaphorase-positive nerve fibres than controls but less than in the sham group. CONCLUSION: Bilateral cavernosal nerve freezing causes erectile dysfunction with accompanying neurological changes. Intracavernosal injection with either VEGF or AAV-BDNF alone enhances nerve regeneration, with combined therapy (VEGF and AAV-BDNF) promoting neural and erectile recovery additively.