Effect of electroacupuncture on the degradation of collagen in pelvic floor supporting tissue of stress urinary incontinence rats.

INTRODUCTION AND HYPOTHESIS: To examine the changes induced by electroacupuncture in stress urinary incontinence (SUI) rats, including the urodynamics and collagen degradation-related cytokine molecular biological expression changes, and to explore the effect and mechanism of EA treatment in SUI. METHODS: Female SPF Sprague-Dawley rats were randomly assigned to five groups (n = 10): sham, model, electroacupuncture control, electroacupuncture, and blocker. The leak point pressure (LPP) and maximum bladder capacity (MBC) were measured for each group of rats, and collagen I, collagen III, matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinase (TIMPs) in the anterior vaginal wall of rats in each group were determined by reverse transcription-polymerase chain reaction and western blotting. The data were analyzed by one-way analysis of variance or Kruskal-Wallis test. RESULTS: Electroacupuncture Shenshu (BL23) and Huiyang (BL35) increased the LPP and MBC in SUI rats (P < 0.05). Electroacupuncture treatment significantly increased the protein expression of collagen I and collagen III in the anterior vaginal wall of SUI rats (P < 0.05) and significantly reduced the protein expression of MMP1, MMP2, and MMP9 (P < 0.05). CONCLUSIONS: Electroacupuncture stimulation can alleviate the signs of SUI, and its mechanism is related to the degradation of collagen in the anterior vaginal wall.

Brain derived neurotrophic factor mediates accelerated recovery of regenerative electrical stimulation in an animal model of stress urinary incontinence.

OBJECTIVE: Stress urinary incontinence (SUI) is prevalent among older women and can result from insufficient regeneration of the pudendal nerve (PN). Electrical stimulation (ES) of the PN upregulates brain derived neurotrophic factor (BDNF) and accelerates regeneration. Using tyrosine kinase B (TrkB) to reduce the availability of free BDNF, the aim of this study was to determine if BDNF is necessary for accelerated recovery via ES in a model of SUI. METHODS: Our SUI model consists of Female Sprague-Dawley rats, whose PNs were crushed bilaterally twice for 30 s, followed by insertion of a modified Foley catheter into the vagina with balloon inflation for 4 h. These rats were divided into 4 groups: 1) Sham PN crush and sham vaginal distension without electrode implantation and with saline treatment (sham injury); 2) SUI with sham stimulation and saline treatment (SUI); 3) SUI and ES with saline treatment (SUI&ES); and 4) SUI and ES with TrkB treatment (SUI&ES&TrkB). Animals underwent ES or sham stimulation four times a week for two weeks. Four weeks after injury, animals underwent functional testing consisting of leak point pressure (LPP) with simultaneous external urethral sphincter (EUS) electromyography (EMG) and pudendal nerve recordings. Data was analyzed using ANOVA with Holm-Sidak posthoc test (p < 0.05). EUS and PN specimen were sectioned and stained to semi-quantitatively evaluate morphology, regeneration, and reinnervation. RESULTS: LPP and EUS EMG firing rate were significantly increased in the sham injury and SUI&ES groups compared to the SUI and SUI&ES&TrkB groups. EUS of SUI rats showed few innervated neuromuscular junctions compared to sham injured rats, while both treatment groups showed an increase in reinnervated neuromuscular junctions. CONCLUSION: ES accelerates functional recovery via a BDNF-mediated pathway in a model of SUI. These findings suggest ES could be used as a potential regenerative therapy for women with SUI.

Electrical stimulation enhances neuronal cell activity mediated by Schwann cell derived exosomes.

Electrical stimulation (ES) therapy has good effects in patients with nervous system injury-related diseases. ES promotes nerve cell regeneration and stimulates Schwann cells to express neurotrophic factors. The incidence of stress urinary incontinence (SUI) among elderly people is increasing. Some studies suggest that damage to the pudendal nerve is closely related to the pathogenesis of SUI. It has also been found that pelvic ES can reduce SUI symptoms in a rat model of SUI caused by pudendal nerve injury. Clinically, pelvic floor electrical stimulation is effective in patients with mild to moderate SUI. These studies indicate that ES may ameliorate damage to the pudendal nerve and thus achieve the goal of SUI treatment, although the mechanism of action of this treatment remains unclear. Therefore, the purpose of the present study was to clarify the relationships among ES, neural cells and Schwann cells at the cellular level. We applied ES to nerve cells at 100 mV/mm or 200 mV/mm for 0, 0.5, 1, or 2 h to investigate changes in nerve cell activity. We then co-cultured the nerve cells with Schwann cells to explore the influence of single-culture and co-culture conditions on the nerve cells. Compared to non-ES, ES of the nerve cells increased their activity. Compared to those in single culture, co-cultured nerve cells exhibited an additional increase in activity. We also found that Schwann cell derived exosomes could promote the activity of nerve cells, with glutamate and calcium ions playing a potential role in this process. These results suggest that the mutual regulation of neural cells and Schwann cells plays an important role in the process by which ES ameliorates neurological function, which may provide a basis for subsequent studies.

Electrical stimulation of the pudendal nerve promotes neuroregeneration and functional recovery from stress urinary incontinence in a rat model.

The pudendal nerve can be injured during vaginal delivery of children, and slowed pudendal nerve regeneration has been correlated with development of stress urinary incontinence (SUI). Simultaneous injury to the pudendal nerve and its target muscle, the external urethral sphincter (EUS), during delivery likely leads to slowed neuroregeneration. The goal of this study was to determine if repeat electrical stimulation of the pudendal nerve improves SUI recovery and promotes neuroregeneration in a dual muscle and nerve injury rat model of SUI. Rats received electrical stimulation or sham stimulation of the pudendal nerve twice weekly for up to 2 wk after injury. A separate cohort of rats received sham injury and sham stimulation. Expression of brain-derived neurotrophic factor (BDNF) and ßII-tubulin expression in Onuf's nucleus were measured 2, 7, and 14 days after injury. Urodynamics, leak point pressure (LPP), and EUS electromyography (EMG) were recorded 14 days after injury. Electrical stimulation significantly increased expression of BDNF at all time points and ßII-tubulin 1 and 2 wk after injury. Two weeks after injury, LPP and EUS EMG during voiding and LPP testing were significantly decreased compared with sham-injured animals. Electrical stimulation significantly increased EUS activity during voiding, although LPP did not fully recover. Repeat pudendal nerve stimulation promotes neuromuscular continence mechanism recovery possibly via a neuroregenerative response through BDNF upregulation in the pudendal motoneurons in this model of SUI. Electrical stimulation of the pudendal nerve may therefore improve recovery after childbirth and ameliorate symptoms of SUI by promoting neuroregeneration after injury.

[Outcomes of ER:YAG LASER treatment of stress urinary incontinence in women].

AIM: To evaluate the effectiveness of a new method of treatment for stress urinary incontinence in women using an ER: YAG laser in SMOOTH mode and investigate pathophysiological and pathomorphological changes induced by erbium laser. MATERIALS AND METHODS: This study comprised 98 women aged 37-63 years, who between 2014 and 2016 were diagnosed with SUI (type 1 and 2a, 2b) and grade 0-2 vaginal prolapse. The treatment was performed with a 2940 nm Er:YAG laser (Fotona, Slovenia) using a SMOOTH mode. Clinical assessment included PFIQ-7 and PISQ-12 questionnaires, uroflowmetry, laser Doppler flowmetry and biopsy of the anterior vaginal wall. The examination was carried out at baseline and 1-2 months after the treatment. RESULTS: The effectiveness of treatment was 73%. There was no deterioration after the procedure. Analysis of PFIQ-7 and PISQ-12 questionnaires showed that patients with mild incontinence had the greatest difference between pre- and posttreatment results. Uroflowmetry parameters improved in a majority of patients. Results of laser Doppler flowmetry demonstrated the improvement of blood flow in the microvascular bed. An important feature of the vaginal biopsy after laser exposure was an increase in neoangiogenesis. DISCUSSION: The findings of questionnaires and clinical evaluation of patients with SUI and vaginal prolapse before and after treatment with Er: YAG laser showed high therapeutic effectiveness of this treatment modality. CONCLUSION: Clinical effectiveness of ER: YAG laser in SMOOTH mode was 73%. Patients with type 1 and 2a SUI and mild or moderate incontinence have the best prognosis after treatment with this method.

Therapeutic Effect and Mechanism of Electrical Stimulation in Female Stress Urinary Incontinence.

OBJECTIVE: To investigate the therapeutic effect and underlying molecular mechanism of electrical stimulation (ES) in a murine stress urinary incontinence (SUI) model. MATERIALS AND METHODS: Sixty female C57BL/6 mice were divided into 4 groups: CON group, no intervention; VD group, vaginal distension (VD) with an 8-mm dilator for 1 hour; VD + ES 20 group, 20 Hz ES for 0.5 hour for 7 days after VD; and VD + ES 50 group, 50 Hz ES for 7 days after VD. For functional studies, assessments of urodynamics and sneezing test were performed; then, anterior vaginal wall specimens were collected. Pathological changes were validated by Masson's trichrome and Van Gieson staining, and the expressions of collagen, transforming growth factor (TGF)-ß1-Smad2/3 pathway components, and T-type calcium channels were detected by Western blotting and reverse transcription polymerase chain reaction. RESULTS: ES significantly increased maximum bladder capacity, leak point pressure, and sneezing positive rate in SUI mice. The staining results showed that collagen was disorganized in the VD group but became organized after ES, especially at 50 Hz. The same results were found for collagens I and III. The expression of TGF-ß1, p-Smad2 and p-Smad3 significantly decreased in the VD group and significantly increased in the VD + ES groups, especially in the VD + ES 50 group. The expression of 2 T-type calcium channel subtypes (Cav 3.1 and Cav 3.2) decreased in the VD group compared with the CON group, but increased in the VD + ES group compared with the VD group. CONCLUSION: Dysregulation of collagen metabolism is involved in the pathogenesis of SUI. ES can ameliorate the symptoms of SUI by activating collagen regeneration through the TGFß1-Smad2/3 pathway. T-type calcium channels might be involved in these processes.