The effect of adeno-associated virus mediated brain derived neurotrophic factor in an animal model of neurogenic impotence.

Abstract

We tested the hypothesis that transfecting penile tissue with brain derived neurotrophic factor may facilitate neural recovery and erectile capability after cavernous nerve injury. Of the 34 Sprague-Dawley rats used 10 underwent sham operation and 24 underwent bilateral cavernous nerve freezing and intracavernous injection of adeno-associated virus-LacZ (12) or adeno-associated virus-brain derived neurotrophic factor (12). Erectile function was assessed by cavernous nerve electrostimulation at 4 and 8 weeks, and samples of penile tissue and the major pelvic ganglia were evaluated histologically. In the brain derived neurotrophic factor group mean maximal intracavernous pressure plus or minus standard deviation was significantly higher than in the LacZ group at 4 and 8 weeks (58.5 +/- 11.7 cm. water versus 28.4 +/- 5.5 and 61.3 +/- 12.5 versus 37.7 +/- 7.9, respectively). In addition, in the brain derived neurotrophic factor group reduced nicotinamide adenine dinucleotide phosphate diaphorase staining and neuronal nitric oxide synthase immunostaining revealed significantly more positive nerve fibers in the dorsal nerves and cavernous tissue than in the LacZ group at each time point and the percent of neuronal nitric oxide synthase positive neurons in the major pelvic ganglia was also significantly greater. Moreover, in the LacZ group most neurons showed a light staining pattern with irregular contours and numerous vacuoles in the cytoplasm. Intracavernous injection of adeno-associated virus-brain derived neurotrophic factor may prevent the degeneration of neuronal nitric oxide synthase containing neurons in the major pelvic ganglia and facilitate the regeneration of neuronal nitric oxide synthase containing nerve fibers in penile tissue, thus, enhancing the recovery of erectile function after bilateral cavernous nerve injury.