The effect of vascular endothelial growth factor and brain‐derived neurotrophic factor on cavernosal nerve regeneration in a nerve‐crush rat model

• Published in: BJU international 2003-09, Vol.92 (4), p.470-475
• Main Authors: Hsieh, P.‐S., Bochinski, D.J., Lin, G.T., Nunes, L., Lin, C.S., Lue, T.F.
• Format: Article
• Language: English
• Subjects: Animals; BDNF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - administration & dosage; Erectile Dysfunction - drug therapy; Gynecology. Andrology. Obstetrics; impotence; Male; Male genital diseases; Medical sciences; Models, Animal; nerve regeneration; Nerve Regeneration - drug effects; Non tumoral diseases; Rats; Rats, Sprague-Dawley; Trauma, Nervous System - drug therapy; Vascular Endothelial Growth Factor A - administration & dosage; VEGF
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1046/j.1464-410X.2003.04373.x

OBJECTIVE To test the hypothesis that an intracavernosal injection with brain‐derived neurotrophin factor (BDNF) and vascular endothelial growth factor (VEGF) can facilitate nerve regeneration and recovery of erectile function after cavernosal nerve injury. MATERIALS AND METHODS The study included 25 Sprague‐Dawley rats; four had a sham operation, seven bilateral nerve crushing with no further intervention, and 14 bilateral nerve crushing with either an immediate (seven) or delayed for 1 month (seven) intracavernosal injection with BDNF+VEGF. Erectile function was assessed by cavernosal nerve electrostimulation at 3 months, and neural regeneration by NADPH‐diaphorase staining and tyrosine hydroxylase (TH) staining of penile tissue and major pelvic ganglia (MPG). RESULTS After nerve crushing, the functional evaluation at 3 months showed a lower mean (sd) intracavernosal pressure (ICP) with cavernosal nerve stimulation, at 33.9 (15.3) cmH2O, than in the sham group, at 107.8 (18.1) cmH2O. With an immediate injection with BDNF+VEGF the ICP was significantly higher than in the controls, at 67.8 (38.5) cmH2O. Even delayed injection with BDNF+VEGF improved the ICP, to 78.0 (21.8) cmH2O. Histological analysis of specimens stained for NADPH and TH showed a significant change in the morphology of terminal branches of the cavernosal and dorsal nerves, and the staining quality of the neurones in the MPG. The number of positively stained nerve fibres tended to revert to normal after treatment with BDNF+VEGF. CONCLUSION An intracavernosal injection with BDNF+VEGF appears to both prevent degeneration and facilitate regeneration of neurones containing neuronal nitric oxide synthase in the MPG, dorsal nerve and intracavernosal tissue. Therefore it might have therapeutic potential for enhancing the recovery of erectile function after radical pelvic surgery.