Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model

Huixi Li; Melanie P Matheu; Fionna Sun; Lin Wang; Melissa T Sanford; Hongxiu Ning; Lia Banie; Yung-Chin Lee; Zhongcheng Xin; Yinglu Guo; Guiting Lin; Tom F Lue

doi:10.1016/j.jsxm.2015.11.008

Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model

J Sex Med. 2016 Jan;13(1):22-32. doi: 10.1016/j.jsxm.2015.11.008.

Authors

Huixi Li¹, Melanie P Matheu², Fionna Sun³, Lin Wang¹, Melissa T Sanford³, Hongxiu Ning³, Lia Banie³, Yung-Chin Lee⁴, Zhongcheng Xin⁵, Yinglu Guo⁵, Guiting Lin³, Tom F Lue⁶

Affiliations

¹ Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA; Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, Beijing, P.R. China.
² Diabetes Center, University of California, San Francisco, CA, USA.
³ Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
⁴ Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA; Department of Urology, Kaohsiung Medical University Hospital, Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁵ Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, Beijing, P.R. China.
⁶ Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA. Electronic address: tlue@urology.ucsf.edu.

PMID: 26755082
DOI: 10.1016/j.jsxm.2015.11.008

Abstract

Introduction: Erectile dysfunction (ED) caused by pelvic injuries is a common complication of civil and battlefield trauma with multiple neurovascular factors involved, and no effective therapeutic approach is available.

Aims: To test the effect and mechanisms of low-energy shock wave (LESW) therapy in a rat ED model induced by pelvic neurovascular injuries.

Methods: Thirty-two male Sprague-Dawley rats injected with 5-ethynyl-2'-deoxyuridine (EdU) at newborn were divided into 4 groups: sham surgery (Sham), pelvic neurovascular injury by bilateral cavernous nerve injury and internal pudendal bundle injury (PVNI), PVNI treated with LESW at low energy (Low), and PVNI treated with LESW at high energy (High). After LESW treatment, rats underwent erectile function measurement and the tissues were harvested for histologic and molecular study. To examine the effect of LESW on Schwann cells, in vitro studies were conducted.

Main outcome measurements: The intracavernous pressure (ICP) measurement, histological examination, and Western blot (WB) were conducted. Cell cycle, Schwann cell activation-related markers were examined in in vitro experiments.

Results: LESW treatment improves erectile function in a rat model of pelvic neurovascular injury by leading to angiogenesis, tissue restoration, and nerve generation with more endogenous EdU(+) progenitor cells recruited to the damaged area and activation of Schwann cells. LESW facilitates more complete re-innervation of penile tissue with regeneration of neuronal nitric oxide synthase (nNOS)-positive nerves from the MPG to the penis. In vitro experiments demonstrated that LESW has a direct effect on Schwann cell proliferation. Schwann cell activation-related markers including p-Erk1/2 and p75 were upregulated after LESW treatment.

Conclusion: LESW-induced endogenous progenitor cell recruitment and Schwann cell activation coincides with angiogenesis, tissue, and nerve generation in a rat model of pelvic neurovascular injuries.

Keywords: Angiogenesis; Endogenous Progenitor Cells; Erectile Dysfunction; Low Energy Shock Wave; Nerve Regeneration; Schwann Cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Blotting, Western
Deoxyuridine / analogs & derivatives
Deoxyuridine / metabolism
Disease Models, Animal
Erectile Dysfunction / pathology*
Erectile Dysfunction / therapy*
Male
Nitric Oxide Synthase Type I / metabolism
Pelvis / injuries
Pelvis / pathology*
Penile Erection
Penis / pathology*
Prostatectomy / adverse effects
Rats
Rats, Sprague-Dawley
Schwann Cells / metabolism*
Trauma, Nervous System / pathology*
Ultrasonic Therapy*

Substances

Nitric Oxide Synthase Type I
5-ethynyl-2'-deoxyuridine
Deoxyuridine