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.


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.


CONCLUSIONS
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.
Chen
Kuo-Chiang
KC
Department of Urology, University of California San Francisco, San Francisco, CA, USA.
Minor
Thomas X
TX
Rahman
Nadeem U
NU
Ho
Hao-Chung
HC
Nunes
Lora
L
Lue
Tom F
TF
D000256:Adenoviridae; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy*; D007267:Injections; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020196:Trauma, Nervous System; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A