We recently demonstrated that treatment with the 5-HT(1A/7) receptor agonist [(R)-(+)-8-hydroxy-2-di-n-propylamino]tetralin (8-OH-DPAT) increases bladder capacity in chloralose-anesthetized female cats with chronic spinal cord injury. In the current study, we investigated the effects of 8-OH-DPAT on bladder capacity and external urethral sphincter (EUS) activity in urethane-anesthetized female rats (initial body mass 175-200 g) with chronic spinal cord injury (transsection at T10). Cystometric study took place 8-12 wk posttranssection. Intravesical pressure was monitored in urethane-anesthetized rats with a transvesical catheter, and EUS activity was assessed electromyographically. Spinal cord injury disrupts phasic activity of the EUS, resulting in decreased voiding efficiency and increased residual volume. 8-OH-DPAT induced a dose-dependent decrease in bladder capacity (the opposite of its effect in chronic spinal cord-injured cats) with an increase in micturition volume and decrease in residual volume resulting from improvement in voiding efficiency. The unexpected improvement in voiding efficiency can be explained by the 8-OH-DPAT-induced emergence of phasic EUS relaxation. Phasic EUS relaxation was also altered by 8-OH-DPAT in spinally intact rats, whereas the 5-HT(1A) receptor antagonist N-tert-butyl-3-[4-(2-methoxyphenyl)-piperazin-1-yl]-2-phenylpropanamide (WAY-100635), on its own, was without effect. It remains to be determined when phasic relaxation is restored after spinal cord injury, and indeed whether it is ever truly lost or is only temporarily separated from excitatory input.

Use of a 2 μm CW thulium laser is feasible and effective in treating primary NMIBC. With a cystoscopic biopsy of the bladder muscle, 2 μm CW thulium laser could retrieve sufficient diagnostic and prognostic specimens.

Background/Aims: To evaluate whether local injection of exosomes derived from human adipose-derived stem cells (hADSCs) facilitates recovery of stress urinary incontinence (SUI) in a rat model. Methods: For the in vitro study, a Cell Counting Kit-8 (CCK-8) array and proteomic analysis were performed. For the in vivo study, female rats were divided into four groups: sham, SUI, adipose-derived stem cell (ADSC), and exosomes (n = 12 each). The SUI model was generated by pudendal nerve transection and vaginal dilation. Vehicle, hADSCs, or exosomes were injected into the peripheral urethra. After 2, 4, and 8 weeks, the rats underwent cystometrography and leak point pressure (LPP) testing, and tissues were harvested for histochemical analyses. Results: The CCK-8 experiment demonstrated that ADSC-derived exosomes could enhance the growth of skeletal muscle and Schwann cell lines in a dose-dependent manner. Proteomic analysis revealed that ADSC-derived exosomes contained various proteins of different signaling pathways. Some of these proteins are associated with the PI3K-Akt, Jak-STAT, and Wnt pathways, which are related to skeletal muscle and nerve regeneration and proliferation. In vivo experiments illustrated that rats of the exosome group had higher bladder capacity and LPP, and had more striated muscle fibers and peripheral nerve fibers in the urethra than rats of the SUI group. Both urethral function and histology of rats in the exosome group were slightly better than those in the ADSC group. Conclusions: Local injection of hADSC-derived exosomes improved functional and histological recovery after SUI.

Serotonin (5-HT) receptors are widely distributed in the central nervous system, including several areas involved in the control of micturition reflex pathways. However, the roles of the different subtypes of 5-HT receptors are not well known. We studied in normal, conscious rats, the effects on the cystometrogram of intracerebroventricular (i.c.v.) administration of 5-HT, 8-hydroxy-2-(di-N-propylaminotetralin) (8-OH-DPAT; agonist at 5-HT(1A) receptors), alpha-methyl-5-hydroxytryptamine maleate (agonist at 5-HT(2) receptors), 2-methyl-5-hydroxytryptamine hydrochloride (agonist at 5-HT(3) receptors), and 1-(4-amino-5-chloro-2methoxyphenyl)-3-(1-n-butyl-4piperidinyl)-1-propanone hydrochloride (RS67506; agonist at 5-HT(4) receptors). Female Sprague-Dawley rats, weighing approximately 230 g, were used. A polyethylene catheter was inserted into the bladder through the dome for cystometric investigations. For administration of drugs, a catheter was implanted into the right cerebral ventricle. Three days after implantation of the bladder catheter, continuous cystometry was performed. Administration of 5-HT (6 nmol/kg i.c.v.), 8-OH-DPAT (6 nmol/kg), alpha-methyl-5-hydroxytryptamine maleate (6 nmol/kg), or RS67506 hydrochloride (6 nmol/kg) significantly (P < 0.05) increased micturition pressure and decreased bladder capacity and micturition volume. The effects increased in a dose-dependent manner (18, 60 nmol/kg). Intracerebroventricular administration of 2-methyl-5-hydroxytryptamine hydrochloride (60 nmol/kg) caused no change in the cystometric parameters. The results suggest that in normal conscious rats, at the supraspinal level, 5-HT (via 5-HT(1A), 5-HT(2), and 5-HT(4) receptors) can enhance the micturition reflex induced by bladder filling. Whether this means that 5-HT(1A), 5-HT(2), and 5-HT(4) receptors can be targets for drugs meant for treatment of bladder hyperactivity, should be explored.