The urethral continence mechanism during passive increments in intravesical pressure (Pves) was investigated by microtip transducer catheters in urethaneanesthetized female rats. Following acute spinal cord transection (Th89) that prevented reflex bladder contractions, when Pves was clamped at 20, 40 or 60cmH2O for 2 minutes, a restricted portion of the middle to proximal urethra (12.515 mm from the urethral orifice) showed contractile responses that were abolished by cutting the pelvic nerves (PN) bilaterally. In PNintact rats, bilateral transection of either pudendal nerves, nerves to iliococcygeous/pubococcygeous muscles or hypogastric nerves significantly reduced the urethral contractile response induced by passive Pves increases, and combined transection of these three sets of nerves totally abolished the urethral closing responses. Similar magnitude of urethral contractile responses during passive Pves elevation to 20 to 40 cmH2O was also observed in spinal intact rats when the response was measured ...

Increased motor nerve latency in women with stress urinary incontinence (SUI) suggests that pudendal nerve (PN) function and recovery are important to the multifactorial continence mechanism. A PN crush (PNC) model of SUI in female rats demonstrates tha...

Stress urinary incontinence (SUI) is a prevalent disorder affecting 30% of women over the age of 40. The primary risk factor for SUI is childbirth which injures both the pudendal nerve and the muscle it innervates: the external urethral sphincter, creat...

Stress urinary incontinence (SUI) is the involuntary loss of urine on exertion due to impaired urethral tone. Drugs which enhance serotonergic and adrenergic drive and urethral function in pre-clinical animal models are effective in treating SUI, but are known to have undesirable side-effects such as nausea. Presently, in dog sacral spinal cord, we identified Onuf’s nucleus (ON), which is known to contain neurones responsible for the somatic innervation of the external urethral sphincter (EUS), and utilised laser `capture micro-dissection and reverse transcriptase-polymerase chain reaction techniques to show high levels of 5-HT2C receptors within these neurones. Subsequently, we investigated the effects of known 5-HT2C agonists mCPP, Ro 60-0175 and YM 348 in guinea pig and canine models of urethral function. In terminally anaesthetised female guinea pigs all agonists (0.01- 1 mg kg-1 iv.) induced dose-dependent increases in EUS electromyographic (EMG) activity during normal bladder filling, compared to con...

Stress Urinary Incontinence (SUI) is correlated with pudendal nerve injury and resultant denervation of the external urethral sphincter (EUS) after vaginal delivery. Symptoms of SUI typically surface during menopause, suggesting hormonal participation in its etiology. Estrogen is also a potent neuroregenerative agent and might be useful to promote recovery from nerve injury. In the present study, we sought to pinpoint the time, relative to pudendal nerve injury, that estrogen (E2) administration would have its greatest effect. The pudendal nerve was crushed in 58 ovariectomized virgin rats and 22 rats were used as sham controls. E2 was administered subcutaneously 6 days prior to nerve crush (n=14), at the time of nerve crush (n=16), or 2 days after nerve crush (n=14). Sham implants were given at the time of nerve crush (n=14). Seven days after nerve crush, the rats were anesthetized for leak point pressure testing. Gentle pressure was applied to each rat's abdomen and was slowly increased until leakage of ...

Chronic implantable probes fabricated using Michigan silicon technology have been used extensively in central nervous system (CNS) applications. In this study, we have developed surgical techniques and have proposed to modify the interconnect system sui...

During vaginal childbirth, the muscles, nerves and ligaments of the pelvic floor are compressed and injured. These injuries are strongly correlated with later development of stress urinary incontinence (SUI). Neurotrophins are upregulated after nerve in...

The Enhanced-Deep-Super-Resolution (EDSR) model is a state-of-the-art convolutional neural network suitable for improving image spatial resolution. It was previously trained with general-purpose pictures and then, in this work, tested on biomedical magnetic resonance (MR) images, comparing the network outcomes with traditional up-sampling techniques. We explored possible changes in the model response when different MR sequences were analyzed. T1w and T2w MR brain images of 70 human healthy subjects (F:M, 40:30) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository were down-sampled and then up-sampled using EDSR model and BiCubic (BC) interpolation. Several reference metrics were used to quantitatively assess the performance of up-sampling operations (RMSE, pSNR, SSIM, and HFEN). Two-dimensional and three-dimensional reconstructions were evaluated. Different brain tissues were analyzed individually. The EDSR model was superior to BC interpolation on the selected metrics, both for two- ...

Stress urinary incontinence (SUI) affects primarily elderly women and has a complex etiology, including pudendal nerve injury and decreasing estrogen levels. The pudendal nerve innervates the external urethral sphincter (EUS), which helps maintain urinary continence. Our goal was to determine the early effects of estrogen depletion/supplementation on the pudendal nerve following a bilateral crush injury. Virgin female rats (n=15) were ovariectomized and underwent a bilateral pudendal nerve crush injury. Seven rats (E group) received a subcutaneous estrogen-containing capsule and eight rats (S group) received a saline sham subcutaneous capsule. After two weeks the rats were euthanized and the pudendal nerves were prepared for light and electron microscopy. Under oil immersion, the myelinated axons, large myelinated axons (> 6 μm), myelin figures, large unmyelinated axons (>1 μm), and endoneurial nuclei were counted in the right EUS branch. Student's t-test determined statistical significance (p<0.05) betwee...

Adult hippocampal neurogenesis is to a large degree controlled at the level of cell survival, and a number of potential mediators of this effect have been postulated. Here, we investigated the small heat shock protein Hspb8, which, because of its pleiotropic prosurvival effects in other systems, was considered a particularly promising candidate factor. Hspb8 is, for example, found in plaques of Alzheimer disease but exerts neuroprotective effects. We found that expression of Hspb8 increased during differentiation in vitro and was particularly associated with later stages (48–96 h) of differentiation. Gain-of-function and loss-of-function experiments supported the hypothesis that Hspb8 regulates cell survival of new neurons in vitro . In the dentate gyrus of adult mice in vivo , lentiviral overexpression of Hspb8 doubled the surviving cells and concomitantly promoted differentiation and net neurogenesis without affecting precursor cell proliferation. We also discovered that the truncated form of the crystal...