Login to Access Video or Poster Abstract: MP45-08
Sources of Funding: NIH/NIDDK: DK079184

Introduction

Seventy-two percent of prostatectomy patients develop stress urinary incontinence (SUI) in the first week after surgery, and individuals who do not recover within 6 months, generally do no regain function without intervention (44%). Preoperative erectile function predicts post-prostatectomy continence and SUI recovery correlates with neurovascular bundle sparing, suggesting the importance of maintaining neural innervation. The hypogastric (HGN) and pelvic nerves (PN) control bladder neck and bladder contraction/relaxation. We hypothesize that the HPG and PN may be injured during prostatectomy, in a similar manner to cavernous nerve (CN) injury, and thus contribute to post-prostatectomy SUI development. We will examine HPG, PN and CN architecture and signaling in normal pelvic ganglia and in a rat prostatectomy model.

Methods

The pelvic plexus in normal (n=9), sham (n=6) and CN crushed (n=20) adult Sprague Dawley rats was examined for apoptotic index and sonic hedgehog (SHH) pathway signalling by immunohistochemical analysis for cleaved caspase-3 (apoptosis indicator), -8, -9, SHH and its receptors Patched and Smoothened.

Results

Cleaved caspase-3 was present in normal pelvic plexus and increased in the CN and PN with CN injury. Cleaved caspase-3 was identified primarily in glial cells surrounding PG neurons and in Schwann cells of the CN, at 4 days after CN injury, and in Schwann cells of the PN. Caspase-8 increased in PG/CN neurons and glia and in the PN. Caspase-9 was increased in CN Schwann cells but not in PN. SHH and its receptor patched were present in PN neurons, glia and Schwann cells, and HGN neurons and Schwann cells.

Conclusions

Interruption of CN innervation, as occurs in the majority of prostatectomy patients, results in induction of apoptosis in other regions of the pelvic plexus including the PN, thus affecting neural regulation of continence. Identification of HGN and PN contribution to SUI identifies novel treatment avenues for intervention. Involvement of the SHH pathway in maintaining HGN and PN morphology and function is significant, and there is potential for application of peptide amphiphile hydrogel SHH delivery to regenerate nerve function and prevent SUI.

Funding

NIH/NIDDK: DK079184