T. Gevaert

Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro

BACKGROUNDnPreviously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking.nnnAIMnTo evaluate the neurotropic effects of galanin receptor agonists and antagonists inxa0vitro in nitrergic neurons and MPG and inxa0vivo in rats after BCNI.nnnMETHODSnMale Sprague-Dawley rats underwent BCNI and sham surgery. Organ culture and single-cell neuron culture of the MPG were performed. Osmotic pump treatment with the galanin agonist inxa0vivo and measurement of erectile response to electrostimulation after BCNI, immunohistochemical localization of galanin and receptors in the human neurovascular bundle, and myographic analysis of rat corpus cavernosum smooth muscle relaxation to galanin receptor agonists were investigated.nnnOUTCOMESnNeurite outgrowth inxa0vitro and erectile response to electrostimulation after BCNI inxa0vivo, immunohistochemical localization of galanin and receptors, and penile muscle relaxation inxa0vitro.nnnRESULTSnGalanin showed neurotrophic action inxa0vitro and inhibition of endogenous galanin significantly impaired neurite outgrowth in nitrergic but not in sympathetic MPG neurons. Inxa0vivo administration of a selective galanin receptor-2 agonist, M1145, resulted in partial recovery of erectile function (EF) after BCNI. Galanin did not act as a direct vasodilator on corpus cavernosum muscle strips.nnnCLINICAL TRANSLATIONnEndogenous neurotrophins such as galanin could be used as a strategy to improve EF for patients after BCNI from radical prostatectomy.nnnSTRENGTHS AND LIMITATIONSnWe evaluated the effect of galanin on nerve regeneration and EF recovery inxa0vivo and inxa0vitro. Limitations include the lack of washout period for the inxa0vivo experiment and absence of differences in the expression of neuronal markers between treatment groups.nnnCONCLUSIONSnWe identified galanin as a potential endogenous mechanism for nerve regeneration after BCNI, which could play a physiologic role in EF recovery after radical prostatectomy. Inxa0vivo treatment with exogenous galanin was beneficial in enhancing EF recovery after BCNI, but further research is necessary to understand the underlying mechanisms. Weyne E, Hannan JL, Gevaert T, etxa0al. Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth Inxa0Vitro. J Sex Med 2018;15:480-491.