scholarly journals Rat Mesenchymal Stem Cell Secretome Promotes Elastogenesis and Facilitates Recovery from Simulated Childbirth Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1395-1406 ◽  
Author(s):  
Charuspong Dissaranan ◽  
Michelle A. Cruz ◽  
Matthew J. Kiedrowski ◽  
Brian M. Balog ◽  
Bradley C. Gill ◽  
...  
Keyword(s):  
Female Rats ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Paracrine Factors ◽  
Pelvic Organs ◽  
Point Pressure ◽  
Urethral Smooth Muscle ◽  
And Function ◽  
Vaginal Distension

Vaginal delivery is a risk factor for stress urinary incontinence (SUI). Mesenchymal stem cells (MSCs) home to injured organs and can facilitate repair. The goal of this study was to determine if MSCs home to pelvic organs after simulated childbirth injury and facilitate recovery from SUI via paracrine factors. Three experiments were performed. Eighteen female rats received vaginal distension (VD) or sham VD and labeled intravenous (IV) MSCs to investigate if MSCs home to the pelvic organs. Whole-organ imaging and immunofluorescence were performed 1 week later. Thirty-four female rats received VD and IV MSCs, VD and IV saline, or sham VD and IV saline to investigate if MSCs accelerate recovery of continence. Twenty-nine female rats received VD and periurethral concentrated conditioned media (CCM), VD and periurethral control media, or sham VD and periurethral control media to investigate if factors secreted by MSCs accelerate recovery from VD. Urethral histology and function were assessed 1 week later. Significantly more MSCs were observed in the urethra, vagina, and spleen after VD compared to sham VD. Continence as measured by leak point pressure (LPP) was significantly reduced after VD in rats treated with saline or control media compared to sham VD but not in those given MSCs or CCM. External urethral sphincter (EUS) function as measured by electromyography (EMG) was not improved with MSCs or CCM. Rats treated with MSCs or CCM demonstrated an increase in elastin fibers near the EUS and urethral smooth muscle more similar to that of sham-injured animals than rats treated with saline or control media. MSCs homed to the urethra and vagina and facilitated recovery of continence most likely via secretion of paracrine factors. Both MSCs and CCM have promise as novel noninvasive therapies for SUI.

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat

2013 ◽  
Vol 305 (9) ◽  
pp. F1332-F1342 ◽  
Author(s):  
Wen-Jia Fan ◽  
Yu-Ting Li ◽  
Jia-Jin Jason Chen ◽  
Shih-Ching Chen ◽  
You Shuei Lin ◽  
...  
Keyword(s):  
Perfusion Pressure ◽  
Sexual Differences ◽  
Female Rats ◽  
Male Rats ◽  
Sexually Dimorphic ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Sphincter Electromyography ◽  
Point Pressure

In this study, we examined the possibility that 5-HT1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and α-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men.

scholarly journals Diabetes slows the recovery from urinary incontinence due to simulated childbirth in female rats

2007 ◽  
Vol 293 (2) ◽  
pp. R950-R955 ◽  
Author(s):  
Ja-Hong Kim ◽  
Xiao Huang ◽  
Guiming Liu ◽  
Courtenay Moore ◽  
James Bena ◽  
...  
Keyword(s):  
Urinary Incontinence ◽  
External Sphincter ◽  
Bladder Capacity ◽  
Diabetic Rats ◽  
Female Rats ◽  
Sprague Dawley ◽  
Leak Point Pressure ◽  
Sprague Dawley Rats ◽  
Point Pressure ◽  
Vaginal Distension

This study was done to test the hypothesis that simulated vaginal birth by vaginal distension (VD) causes more severe urinary incontinence and slower recovery in diabetic rats. After measuring baseline leak point pressure (LPP) in 16 diabetes mellitus (DM) and 16 age- and weight-matched control (Ct) female Sprague-Dawley rats, these animals underwent either VD or sham VD (sham). Four and ten days after the procedures, LPP and conscious cystometry were assessed. Tissues were then harvested and examined by light microscopy. LPP at baseline was equal among all four groups. Four days after VD, LPP in both VD groups dropped to significantly lower levels than in sham rats ( P < 0.001). Moreover, LPP in the DM+VD group was significantly lower than in the Ct+VD group. At 10 days, LPP in the Ct+VD group had recovered to its baseline value, whereas the LPP in the DM+VD group remained significantly reduced. DM rats had larger bladder capacity and longer voiding intervals than Ct rats. Histological findings included more severe damage to the external sphincter striated musculature of the urethra in DM+VD group compared with Ct+VD. In conclusion, these findings suggest that DM causes increased severity and delayed functional recovery from the effects of simulated childbirth.

scholarly journals Effect of a 5-HT1A receptor agonist (8-OH-DPAT) on external urethral sphincter activity in a rat model of pudendal nerve injury

2011 ◽  
Vol 301 (1) ◽  
pp. R225-R235 ◽  
Author(s):  
Shih-Ching Chen ◽  
Chen-Li Cheng ◽  
Wen-Jia Fan ◽  
Jia-Jin Jason Chen ◽  
Chien-Hung Lai ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Rat Model ◽  
Receptor Agonist ◽  
Pudendal Nerve ◽  
Perfusion Pressure ◽  
Urethral Sphincter ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Point Pressure ◽  
Pudendal Nerve Injury

Although serotonergic agents have been used to treat patients with stress urinary incontinence, the characteristics of the external urethral sphincter (EUS) activity activated by 5-HT receptors have not been extensively studied. This study examined the effects of the 5-HT1A receptor agonist, 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), on the EUS-electromyography and resistance of the urethra in a rat model with bilateral pudendal nerve injury (BPNI). Two measurements were utilized to assess the effects of the drug on bladder and urethral functions: the simultaneous recordings of transvesical pressure under isovolumetric conditions [isovolumetric intravesical pressure (IVP)] and urethral perfusion pressure, and the simultaneous recordings of IVP during continuously isotonic transvesical infusion with an open urethra (isotonic IVP) and EUS-electromyography. This study also evaluated the urethral continence using leak point pressure testing. The urethral perfusion pressure and leak point pressure measurements of BPNI rats reveal that 8-OH-DPAT significantly increased urethral resistance during the bladder storage phase, yet decreased resistance during the voiding phase. The entire EUS burst period was significantly prolonged, within which the average silent period increased and the frequency of burst discharges decreased. 8-OH-DPAT also improved the voiding efficiency, as evidenced by the detection of decreases in the contraction amplitude and residual volume, with increases in contraction duration and voided volume. These findings suggest that 8-OH-DPAT not only improved continence function, but also elevated the voiding function in a BPNI rat model.

scholarly journals Dual simulated childbirth injury delays anatomic recovery

2009 ◽  
Vol 296 (2) ◽  
pp. F277-F283 ◽  
Author(s):  
Hui Q. Pan ◽  
James M. Kerns ◽  
Dan L. Lin ◽  
David Sypert ◽  
James Steward ◽  
...  
Keyword(s):  
Pudendal Nerve ◽  
Leak Point Pressure ◽  
External Urethral Sphincter ◽  
Bdnf Expression ◽  
Nerve Crush ◽  
Histological Evidence ◽  
Injury Model ◽  
Point Pressure ◽  
Urethral Function ◽  
Vaginal Distension

A dual childbirth injury model, including vaginal distension (VD) and pudendal nerve crush (PNC), may best represent the injuries seen clinically. The objective of this study was to investigate urethral function, anatomy, and neurotrophin expression after several simulated childbirth injuries. Groups of 140 rats underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury groups had significantly decreased leak-point pressure (LPP) compared with C rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP in all injury groups had recovered to C values. Histological evidence of injury was still evident in the external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD, brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged. BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was upregulated somewhat but not to the same extent as after PNC. Ten days after injury, PNC+VD had the least number of normal nerve fascicles near the EUS, followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer normal nerve fascicles, but without significant differences compared with C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.

Morphological and functional response to injury to the external urethral sphincter - similarities and differences between male and female rats

2014 ◽  
Vol 35 (3) ◽  
pp. 371-376
Author(s):  
Scheila F. C. Nascimento ◽  
Ana Paula S. Bispo ◽  
Katia Ramos Leite ◽  
Helio Plapler ◽  
Claudius Füllhase ◽  
...  
Keyword(s):  
Functional Response ◽  
Female Rats ◽  
Urethral Sphincter ◽  
External Urethral Sphincter ◽  
Male And Female ◽  
Male And Female Rats ◽  
Similarities And Differences

Activation of the external urethral sphincter central pattern generator by a 5-HT1A receptor agonist in rats with chronic spinal cord injury

2007 ◽  
Vol 292 (4) ◽  
pp. R1699-R1706 ◽  
Author(s):  
Paul C. Dolber ◽  
Baojun Gu ◽  
Xiaoyang Zhang ◽  
Matthew O. Fraser ◽  
Karl B. Thor ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Receptor Agonist ◽  
Bladder Capacity ◽  
Female Rats ◽  
Residual Volume ◽  
Urethral Sphincter ◽  
External Urethral Sphincter ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

We recently demonstrated that treatment with the 5-HT1A/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-HT1A 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.

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