Local continuous glial cell derived neurotrophic factor release using osmotic pump promotes parasympathetic nerve rehabilitation in an animal model of cavernous nerve injury induced erectile dysfunction

BACKGROUND: Nerve injury-related erectile dysfunction (ED) is one of the types that respond poorly to conventional ED treatments. Our previous experiments have demonstrated the paracrine of various neurotrophic factors (NTFs) by stem cells or other treatment modalities as a potential mechanism in the recovery of nerve injury-related ED. Glial cell derived neurotrophic factor (GDNF) is one of the essential NTFs for the regeneration of nerve fibers, especially for parasympathetic nerves. The aim of this study is to explore if local continuous GDNF administration is beneficial for the functional and histological recovery of nerve injury induced ED. METHODS: Eight-week-old male Sprague-Dawley rats were used for this study. Rats were randomly grouped into 5: Sham surgery (Sham), bilateral cavernous nerve injury (BCNI) and placebo treatment, BCNI and 0.1 µg/100 µL GDNF treatment (BCNI+GDNF 0.1), BCNI and 1 µg/100 µL GDNF treatment (BCNI+GDNF 1), BCNI and 10 µg/100 µL GDNF treatment (BCNI+GDNF 10). GDNF was administered using an osmotic pump technique which would deliver GDNF locally and continuously for 28 days without the need for external connections or frequent handling of animals. Recovery of sexual function, nerve fibers regeneration, and expression of neurotrophic receptors were examined and compared among groups after the treatment. RESULTS: Local continuous GDNF release treatment increased the average number of intromissions in the sexual behavior test and intracavernous pressure (ICP) in the erectile function test in a dose dependent manner. Osmotic pump implantation induced increased local GDNF concentration and mild inflammatory response. Gene expression of GDNF receptors in major pelvic ganglion (MPG) and nerve regeneration along the urethra were partially promoted by GDNF. These changes were associated with increased nerve fibers especially the parasympathetic nerve fibers in dorsal nerve of penis (DNP) in GDNF treated groups. CONCLUSIONS: In conclusion, our project illustrated the promising effects of local continuous GDNF administration for the functional and histological recovery of nerve injury-induced ED.