AB300. SPR-27 Sonic hedgehog promotes sprouting of neurons in the pelvic ganglia and cavernous nerve during regeneration
Abstract

AB300. SPR-27 Sonic hedgehog promotes sprouting of neurons in the pelvic ganglia and cavernous nerve during regeneration

Ryan Dobbs1, Shawn Choe1, Daniel A. Harrington2, Samuel I. Stupp3, Kevin T. McVary4, Carol A. Podlasek5

1Department of Urology, University of Illinois at Chicago, Chicago, IL 60612, USA; 2Department of Biosciences, Rice University, Houston, TX 77005, USA; 3Simpson-Querrey Institute for BioNanotechnology, Department of Chemistry, Department of Materials Science and Engineering, and Biomedical Engineering, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA; 4Division of Urology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA; 5Department of Urology, Physiology and Bioengineering, University of Illinois at Chicago, Chicago, IL 60612, USA


Objective: We’ve shown in previous studies that sonic hedgehog (SHH) protein delivered by nanoparticle based peptide amphiphile (PA) hydrogels to the cavernous nerve (CN) at the time of crush injury (mimicking prostatectomy), are neuroprotective and promote CN regeneration in a rat model. The mechanism of how SHH promotes CN regeneration is unknown. We hypothesize that SHH promotes sprouting of CN axons, in order to enhance nerve regeneration. We examine this hypothesis in an in vitro organ culture model.

Methods: The caudal portion of the pelvic ganglia (innervates penis) and CN were dissected from adult Sprague Dawley rats (n=47) and placed in Matrigel in growth factor reduced medium and were grown for three to five days. Pelvic ganglia were exposed to Affi-Gel beads containing: (I) SHH protein; (II) 5e1 and cyclopamine SHH inhibitors; and (III) SHH protein delivered by PA. Additional pelvic ganglia/CN tissue underwent CN crush and were exposed to SHH protein or PBS/mouse serum albumin (MSA) protein. Sprouting was evaluated for number of sprouts and their length, and by immunohistochemical analysis for sprouting markers (GAP43 and nNOS).

Results: Sprouting of pelvic ganglia and CN axons was increased with SHH treatment. Sprouts were more abundant, longer in length, with larger arborization of sprouts, in comparison to controls. More sprouting was promoted with SHH treatment of CN injured nerves. The CN had similar sprouting potential at 4 and 9 days after crush injury. Localization of SHH delivery makes a difference in sprouting potential.

Conclusions: The mechanism of how SHH PA treatment promotes CN regeneration, involves enhanced sprouting of pelvic ganglia and CN neurons. Understanding the mechanism of SHH PA action on neuronal tissue is critical for translation to prostatectomy patients and to further enhance regeneration.

Funding Source(s): NIH/NIDDK DK079184

Keywords: Innervation; neural plasticity; sonic hedgehog (SHH); pelvic ganglia; cavernous nerve (CN); immunostaining


doi: 10.21037/tau.2016.s300


Cite this abstract as: Dobbs R, Choe S, Harrington DA, Stupp SI, McVary KT, Podlasek CA. Sonic hedgehog promotes sprouting of neurons in the pelvic ganglia and cavernous nerve during regeneration. Transl Androl Urol 2016;5(Suppl 2):AB300. doi: 10.21037/tau.2016.s300

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