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Objective: To examine the effects of the selective 5‐HT1A receptor agonist, NLX‐112, on urethral function in streptozotocin‐induced diabetic rats. Materials and Methods: Female Sprague–Dawley rats (n = 32) were divided into two groups: rats with type 1 diabetes mellitus (T1DM) and age‐matched normal control rats (NC). T1DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Isovolumetric cystometry and urethral perfusion pressure (UPP) were evaluated 10 weeks postinjection in rats (n = 9 per group). The selective 5‐HT1A receptor antagonist, WAY‐100635 maleate salt, was administered after NLX‐112 hydrochloride dose–response curve was generated (intravenously). The remaining rats were used for immunofluorescence and Western blot assays. Results: Compared to controls, type 1 diabetic rats (T1D rats) had lower maximal intravesical pressure (IP max) and UPP changes. In T1D rats, NLX‐112 hydrochloride (0.003–1.0 mg/kg) induced dose‐dependent decreases in UPP nadir, IP max, high‐frequency oscillations (HFOs) rate; and increases in UPP change and HFOs amplitude. WAY‐100635 maleate salt (0.3 mg/kg) partially or completely reversed the NLX‐112‐induced changes. Immunofluorescence revealed that 5‐HT1A receptors were found in the L6‐S1 spinal cord dorsolateral nucleus, but the expression was significantly higher in the T1D rats. Additionally, Western blot showed there were significantly more 5‐HT1A receptors in the ventral L6‐S1 spinal cord of T1D rats. Conclusions: Urethral dysfunction in T1D rats was improved by NLX‐112. 5‐HT1A receptors were upregulated in the dorsolateral nucleus of L6‐S1 spinal cord in T1D rats. These findings suggest that NLX‐112 may constitute a novel therapeutic strategy to treat diabetic urethral dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of intrathecal (i.t.) serotonin (5‐hydroxytryptamine) 5‐HT7 agonist administration on voiding function in the urethane‐anesthetised rat, and the change in 5‐HT7 receptor (5‐HT7R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI). Materials and methods: In all, 32 female Sprague–Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5‐HT7R‐selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot. Results: LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1–30 μg/kg) induced significant dose‐dependent increases in micturition volume, voiding efficiency, number of high‐frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non‐voiding contractions. The 5‐HT7R antagonist, SB‐269970 (10 μg/kg), partially reversed LP44‐induced changes. Using PRV retrograde tracing and immunofluorescence, 5‐HT7Rs were found in the L6–S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5‐HT7Rs in the ventral L6–S1 spinal cord in SCI rats. Conclusion: A 5‐HT7R agonist, given i.t., improved voiding efficiency in urethane‐anesthetised SCI rats, and the 5‐HT7R was significantly up‐regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5‐HT7R could be a target for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Aims: To fabricate a novel nanoyarn biomaterial via a dynamic liquid electrospinning system, and to simultaneously evaluate whether nanoyarn is capable of being applied as a urinary sling for future clinical transfer. Methods: Nanoyarn was cultured with adipose‐derived stem cells (ADSCs). Cell morphology and function were observed on nanoyarn. Female rats that underwent vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the urinary incontinence model. After 2 weeks, the cells‐sling was fixed to the suburethra. A commercial sling that tension‐free vaginal tape‐obturator (TVT‐O) was used as a control. The urodynamic test for leak point pressure (LPP) and histological tests were used to evaluate the sling's performance in vivo. Results: The nanoyarn possessed beneficial properties and the actin filament from ADSCs, which is very similar to muscle. Rats that underwent VD and BOR maintained a low LPP, whereas the LPP in rats with VD alone recovered to normal levels within 2 weeks. LPP in the nanoyarn group gradually decreased on the three urodynamic tests post‐suburethral surgery, however, the cell‐laden nanoyarn maintained LPP at normal levels for 8 weeks; the TVT‐O group showed a significant increase in LPP at 8 weeks. Cell‐laden nanoyarn was infiltrated with more cells, collagen, and vessels than the controls. Conclusions: The nanoyarn showed sufficient efficacy to maintain LPP in urinary incontinence rat model. In addition, it improved cell infiltration, collagen and muscle development compared to TVT‐O. Thus, the combination of ADSCs and a nanoyarn scaffold could be a promising tissue‐engineered sling for the treatment of urinary incontinence. [ABSTRACT FROM AUTHOR]

Aim: To investigate the value of repeat botulinum toxin A (BTX‐A) injections in patients with neurogenic detrusor overactivity (NDO). Methods: We searched the PubMed, EMBASE, and EBSCO databases for articles published until June 2016. Studies that reported the efficacy and safety of repeat BTX‐A injections for adult patients with NDO were eligible. The effect size for each outcome was calculated as the standardized mean difference ± standard error and 95% confidence interval, and was graded as small, >0.2; moderate, >0.5; or large, >0.8. The outcomes included maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), reflex volume (RV), bladder compliance (BC), quality of life (QOL), and injection interval. Descriptive reviews were performed for urinary incontinence (UI) and adverse events (AEs). Results: Eighteen studies involving 1533 patients whose level of evidence ranged from 3 to 4 were included in this study. We noted non‐significant changes in MCC, MDP, RV, and BC between the first and last injections. Patients who had received ≤4 injections were found to have stable QOL improvements after the first and last injections, whereas patients who had received ≥5 injections were found to have a significant decrease in QOL after the last injection. No significant differences in injection intervals were noted after repeat BTX‐A injections, and the repeat injection failure rate was low. Conclusion: Our study demonstrated that repeat BTX‐A injections allow sustained improvements in patients with NDO. The rate of AEs was stable and low. However, additional high‐quality, large‐scale, and long‐term trials are necessary to establish the efficacy and safety of ≥5 repeat BTX‐A injections. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether the voiding dysfunction caused by spinal cord injury (SCI) in rats can be improved by i.v. administration of the serotonin (5‐HT)2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropanehydrochloride (DOI), and to discuss whether the mechanism can be ascribed to 5‐HT2A and 5‐HT 2C receptor upregulation in lumbosacral cord motoneurons. Materials and Methods: Female Sprague–Dawley rats were divided into two groups (SCI group vs normal control [NC] group). Under urethane anaesthesia, cystometry was performed to examine the variation in urodynamic variables before and after successive intrathecal (i.t.) administration of various doses of DOI into the lumbosacral cord. Changes in 5‐HT2A and ‐2C receptors in the lumbosacral cord were also investigated using immunohistochemical staining and Western blot analysis. Results: Compared with NC rats, the SCI rats had higher bladder capacity and post‐void residual urine volume, and lower voiding efficiency. After SCI, DOI improved voiding efficiency, probably via external urethral sphincter (EUS) activity. Immunohistochemical staining and Western blot analysis showed that 5‐HT2A and ‐2C receptors were upregulated in lumbosacral cord motoneurons. Conclusion: In rats with SCI, DOI can improve voiding efficiency; this may be attributable to 5‐HT2A and ‐2C receptor upregulation in lumbosacral cord motoneurons controlling EUS activity. [ABSTRACT FROM AUTHOR]

Aims: To explore the role of voltage-gated calcium channels (VGCC) in 5-HT 2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5-hydroxy tryptamine (5-HT) 2A receptors and VGCCs in lumbosacral cord after SCI., Methods: Female Sprague-Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS-EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS-EMG. Rats were euthanized and L6-S1 spinal cord were acquired for immunofluorescence., Results: In SCI rats, intrathecal administration of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride or L-type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high-frequency oscillations. They could also prolong EUS bursting activity duration on EUS-EMG. Moreover, the effect of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride can be eliminated with the combined administration of L-type VGCC agonist, (±)-Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T-type VGCC blocker TTA-P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5-HT 2A receptor and Cav1.2 immunolabeling-positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats., Conclusions: Our study demonstrated that 5-HT 2A/2C agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride may improve SCI-induced DSD by inhibiting the L-type voltage-gated calcium channel in lumbosacral cord motoneurons., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Lower urinary tract (LUT) dysfunction is the most common complication of diabetes mellitus (DM). An involvement of the 5-HT 2A receptor in spinal micturition control has been demonstrated in urethane anaesthetized DM rats in which i.v. administration of the 5-HT 2A/2C receptor agonist 2,5-methoxy-4-iodoamphetamine (DOI), stimulated high frequency oscillations (HFOs) and improved micturition. However, the mechanisms involved in these effects are not completely understood. The present work showed that 5-HT 2A and -2C receptors were upregulated in lumbosacral cord motoneurons, and the number of serotonergic paraneurons were downregulated in the urethra in DM group. The importance of the downregulation of urethral paraneurons in DM remains to be elucidated but may be related to the reduced urethral sensation caused by the disease. We suggest that targets of 5-HT receptor agonists for improvement of voiding function may be found both in the LUT and lumbosacral spinal cord., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To examine the effect of intrathecal (i.t.) serotonin (5-hydroxytryptamine) 5-HT 7 agonist administration on voiding function in the urethane-anesthetised rat, and the change in 5-HT 7 receptor (5-HT 7 R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI)., Materials and Methods: In all, 32 female Sprague-Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5-HT 7 R-selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot., Results: LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1-30 μg/kg) induced significant dose-dependent increases in micturition volume, voiding efficiency, number of high-frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non-voiding contractions. The 5-HT 7 R antagonist, SB-269970 (10 μg/kg), partially reversed LP44-induced changes. Using PRV retrograde tracing and immunofluorescence, 5-HT 7 Rs were found in the L6-S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5-HT 7 Rs in the ventral L6-S1 spinal cord in SCI rats., Conclusion: A 5-HT 7 R agonist, given i.t., improved voiding efficiency in urethane-anesthetised SCI rats, and the 5-HT 7 R was significantly up-regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5-HT 7 R could be a target for therapeutic interventions., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to investigate the effects of ketanserin on micturition mediated via the 5-HT 2A receptor in the motoneuron nucleus of the Lumbosacral cord, as reflected in high frequency oscillations (HFOs) of intravesical pressure and the external urethral sphincter electromyogram (EUS-EMG) in anesthetized male rats. METHODS：: Male Sprague-Dawley rats were used. Cystometry and EUS-EMG were performed in all rats under urethane anesthesia to examine the variations after successive intrathecal (i.t.) administration of various doses of ketanserin into the lumbosacral cord. Immunofluorescence staining and Western blotting were made to observe the distribution of 5-HT2 A and -2C receptors in the lumbosacral cord motor neurons., Results: Compared to the controls, ketanserin-treated rats showed a declined trend of dose-dependent manner in the HFOs, in accordance with the variation of EUS-EMG, while decreased micturition volume, voiding efficiency, and increased post-void residual volume was only observed at the dose of 0.1 mg/kg. The effects of ketanserin on the HFO and EUS-EMG activity were partially or completely reversed by the 5-HT 2A/2C receptor agonist, DOI. Meanwhile, immunofluorescence staining and Western blot analysis showed that immunoreactivity of 5-HT 2A receptor was higher than that of 5-HT 2C, labeling in the lumbosacral cord motoneurons., Conclusions: The intrathecally administrated 5-HT 2A receptor antagonist ketanserin can weaken the EUS bursting activity, decrease HFOs, and reduce voiding efficiency as dose dependently. The effects of ketanserin on micturition may be mainly mediated via the 5-HT 2A receptors in the motoneuron nucleus of the lumbosacral cord., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To investigate whether the voiding dysfunction caused by spinal cord injury (SCI) in rats can be improved by i.v. administration of the serotonin (5-HT) 2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropanehydrochloride (DOI), and to discuss whether the mechanism can be ascribed to 5-HT 2A and 5-HT 2C receptor upregulation in lumbosacral cord motoneurons., Materials and Methods: Female Sprague-Dawley rats were divided into two groups (SCI group vs normal control [NC] group). Under urethane anaesthesia, cystometry was performed to examine the variation in urodynamic variables before and after successive intrathecal (i.t.) administration of various doses of DOI into the lumbosacral cord. Changes in 5-HT 2A and - 2C receptors in the lumbosacral cord were also investigated using immunohistochemical staining and Western blot analysis., Results: Compared with NC rats, the SCI rats had higher bladder capacity and post-void residual urine volume, and lower voiding efficiency. After SCI, DOI improved voiding efficiency, probably via external urethral sphincter (EUS) activity. Immunohistochemical staining and Western blot analysis showed that 5-HT 2A and - 2C receptors were upregulated in lumbosacral cord motoneurons., Conclusion: In rats with SCI, DOI can improve voiding efficiency; this may be attributable to 5-HT 2A and - 2C receptor upregulation in lumbosacral cord motoneurons controlling EUS activity., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)