title: Low-energy Shock Wave Therapy Ameliorates Erectile Dysfunction in a Pelvic Neurovascular Injuries Rat Model.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Huixi
authors.initials: H
authors.lastname: Li
authors.affiliation: Diabetes Center, University of California, San Francisco, CA, USA.
authors.forename: Melanie P
authors.initials: MP
authors.lastname: Matheu
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Fionna
authors.initials: F
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Melissa T
authors.initials: MT
authors.lastname: Sanford
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Lia
authors.initials: L
authors.lastname: Banie
authors.affiliation: 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.
authors.forename: Yung-Chin
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, Beijing, P.R. China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Xin
authors.affiliation: Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, Beijing, P.R. China.
authors.forename: Yinglu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA. Electronic address: tlue@urology.ucsf.edu.
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000473:pathology* / Q000628:therapy*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010388:Pelvis / Q000293:injuries / Q000473:pathology*; D010410:Penile Erection; D010413:Penis / Q000473:pathology*; D011468:Prostatectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism*; D020196:Trauma, Nervous System / Q000473:pathology*; D014464:Ultrasonic Therapy
chemical_list: D052248:Nitric Oxide Synthase Type I; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Angiogenesis; Endogenous Progenitor Cells; Erectile Dysfunction; Low Energy Shock Wave; Nerve Regeneration; Schwann Cells