INTRODUCTION: The cavernous nerve (CN) is commonly injured during prostatectomy. Manipulation of the nerve microenvironment is critical to improve regeneration and develop novel erectile dysfunction therapies. Sonic hedgehog (SHH) treatment promotes CN regeneration. The mechanism of how this occurs is unknown. Brain-derived neurotrophic factor (BDNF) facilitates return of erectile function after CN injury and it has been suggested in cortical neurons and the sciatic nerve that BDNF may be a target of SHH. AIM: To determine if SHH promotes CN regeneration through a BDNF-dependent mechanism. METHODS: Sprague Dawley rats underwent (i) bilateral CN crush (N = 15); (ii) SHH treatment of pelvic ganglia (PG)/CN (N = 10); (iii) SHH inhibition in PG/CN (N = 14 rats); (iv) CN crush with SHH treatment of PG/CN (N = 10 rats); (v) CN crush with SHH treatment and BDNF inhibition (N = 14 rats); and (vi) CN injury and SHH treatment of the penis (N = 23). MAIN OUTCOME MEASURES: BDNF and glial fibrillary acidic protein were quantified in PG/CN by Western, and a t-test was used to determine differences. RESULTS: In normal rats SHH inhibition in the PG/CN decreased BDNF 34% and SHH treatment increased BDNF 36%. BDNF was increased 44% in response to SHH treatment of crushed CNs, and inhibition of BDNF in crushed CNs treated with SHH protein hampers regeneration. CONCLUSIONS: SHH regulates BDNF in the normal and regenerating PG/CN. BDNF is part of the mechanism of how SHH promotes regeneration, thus providing an opportunity to further manipulate the nerve microenvironment with combination therapy to enhance regeneration.
INTRODUCTION: The cavernous nerve (CN) is commonly injured during prostatectomy. Manipulation of the nerve microenvironment is critical to improve regeneration and develop novel erectile dysfunction therapies. Sonic hedgehog (SHH) treatment promotes CN regeneration. The mechanism of how this occurs is unknown. Brain-derived neurotrophic factor (BDNF) facilitates return of erectile function after CN injury and it has been suggested in cortical neurons and the sciatic nerve that BDNF may be a target of SHH. AIM: To determine if SHH promotes CN regeneration through a BDNF-dependent mechanism. METHODS:Sprague Dawley rats underwent (i) bilateral CN crush (N = 15); (ii) SHH treatment of pelvic ganglia (PG)/CN (N = 10); (iii) SHH inhibition in PG/CN (N = 14 rats); (iv) CN crush with SHH treatment of PG/CN (N = 10 rats); (v) CN crush with SHH treatment and BDNF inhibition (N = 14 rats); and (vi) CN injury and SHH treatment of the penis (N = 23). MAIN OUTCOME MEASURES: BDNF and glial fibrillary acidic protein were quantified in PG/CN by Western, and a t-test was used to determine differences. RESULTS: In normal ratsSHH inhibition in the PG/CN decreased BDNF 34% and SHH treatment increased BDNF 36%. BDNF was increased 44% in response to SHH treatment of crushed CNs, and inhibition of BDNF in crushed CNs treated with SHH protein hampers regeneration. CONCLUSIONS:SHH regulates BDNF in the normal and regenerating PG/CN. BDNF is part of the mechanism of how SHH promotes regeneration, thus providing an opportunity to further manipulate the nerve microenvironment with combination therapy to enhance regeneration.
Authors: Nicholas L Angeloni; Christopher W Bond; Yi Tang; Daniel A Harrington; Shuming Zhang; Samuel I Stupp; Kevin E McKenna; Carol A Podlasek Journal: Biomaterials Date: 2010-10-23 Impact factor: 12.479
Authors: Anthony J Bella; Guiting Lin; Maurice M Garcia; Kavirach Tantiwongse; William O Brant; Ching-Shwun Lin; Tom F Lue Journal: Eur Urol Date: 2006-10-30 Impact factor: 20.096
Authors: R Kato; D Wolfe; C H Coyle; J B Wechuck; P Tyagi; T Tsukamoto; J B Nelson; J C Glorioso; M B Chancellor; N Yoshimura Journal: Gene Ther Date: 2008-07-31 Impact factor: 5.250
Authors: Guiting Lin; Alan W Shindel; Thomas M Fandel; Anthony J Bella; Ching-Shwun Lin; Tom F Lue Journal: BJU Int Date: 2009-06-02 Impact factor: 5.588
Authors: Stephen S Connolly; James J Yoo; Mohamed Abouheba; Shay Soker; W Scott McDougal; Anthony Atala Journal: World J Urol Date: 2008-07-02 Impact factor: 4.226
Authors: Shuming Zhang; Megan A Greenfield; Alvaro Mata; Liam C Palmer; Ronit Bitton; Jason R Mantei; Conrado Aparicio; Monica Olvera de la Cruz; Samuel I Stupp Journal: Nat Mater Date: 2010-06-13 Impact factor: 43.841
Authors: Johanna L Hannan; Maarten Albersen; Bernard L Stopak; Xiaopu Liu; Arthur L Burnett; Ahmet Hoke; Trinity J Bivalacqua Journal: J Neurosci Res Date: 2015-01-19 Impact factor: 4.164
Authors: E De Felice; I Porreca; E Alleva; P De Girolamo; C Ambrosino; E Ciriaco; A Germanà; P Sordino Journal: J Anat Date: 2014-03-04 Impact factor: 2.610