• Christopher W Bond, Nicholas Angeloni, Daniel Harrington, Samuel Stupp, and Carol A Podlasek.
• Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
• J Sex Med. 2013 Mar 1;10(3):730-7.

IntroductionThe 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.AimTo determine if SHH promotes CN regeneration through a BDNF-dependent mechanism.MethodsSprague 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 MeasuresBDNF and glial fibrillary acidic protein were quantified in PG/CN by Western, and a t-test was used to determine differences.ResultsIn 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.ConclusionsSHH 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.© 2012 International Society for Sexual Medicine.

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