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

Abstract 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 (SUIE 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  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.