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- Aronsson, Patrik, 1983, et al.
(författare)
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A novel in situ urinary bladder model for studying afferent and efferent mechanisms in the micturition reflex in the rat.
- 2014
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Ingår i: Neurourology and urodynamics. - : Wiley. - 1520-6777 .- 0733-2467. ; 33:5, s. 550-557
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The search for new animal models to investigate both efferent and afferent levels of the micturition reflex, to better understand urinary dysfunctions, is of great importance. Therefore in this study we developed and characterized, by comparisons with a conventional whole bladder model, a novel in situ model. METHODS: The urinary bladder was carefully prepared and separated, via a midline incision, into two halves all the way to the urethra in pentobarbitone and medetomidine anesthetized male rats. The separated bladder halves (with no direct connection) were immobilized with ligatures to the underlying tissue. The tension could thereafter be recorded at one side, while the other half was occasionally stretched in order to evoke an afferent signal. Also, injections of ATP and methacholine and electric nerve stimulation were employed. RESULTS: Ipsilateral stretch of 30 and 50mN induced a force-dependent contractile response on the contralateral side. Moreover, electrical stimulation of efferent pelvic nerve fibers, and intravenous injections of methacholine and ATP, evoked dose-dependent contractions, resembling responses observed in the whole bladder model. Here, the threshold frequency at electrical stimulation of the efferent fibers was <2Hz and the maximum response appeared at 10-20Hz, while afferent stimulation had a threshold of 5-10Hz with the maximum response at 40Hz. CONCLUSIONS: In the current study we show that stimulation of afferents at one side of the bladder induces, via impulses from the central nervous system, contractions from the other side. This novel model enables quantitative comparisons of changes occurring within the micturition reflex arc in bladder disorders.
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| 3. |
- Aronsson, Patrik, 1983, et al.
(författare)
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Cyclophosphamide-induced alterations of the micturition reflex in a novel in situ urinary bladder model in the anesthetized rat
- 2015
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467. ; 34:4, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Cyclophosphamide-induced cystitis alterations have been reported to occur both at efferent and afferent level in the micturition reflex arc. In particular, the stretching of the bladder wall causing urothelial release of ATP has been proposed as one of the pivotal mechanisms causing these alterations. To evaluate functional changes at efferent and afferent levels of the micturition reflex following cyclophosphamide treatment we have applied a novel in situ half bladder rat model. Methods: Male Sprague-Dawley rats were treated with either saline or cyclophosphamide (100mg/kg), and stretch-, electric-, methacholine-, and ATP-induced responses were thereafter measured at 60-72hr postinjection under pentobarbitone anesthesia. In the novel in situ half bladder model, the urinary bladder was prepared via a midline incision, where the two halves were separated all the way to the urethra as previously described. Results: Following bladder stretch of 30-80mN, of the half that was not used for tension measurement, the cyclophosphamide-treated animals evoked significant two- to threefold larger contractile responses as compared to saline-treated control animals. A sensitization of the afferent arm was shown in cyclophosphamide-treated animals, since afferent stimulation evoked similar responses as in control animals despite that the efferent pelvic nerve stimulation displayed a lower contraction-frequency relationship in cyclophosphamide-treated animals. Atropine reduced the stretch(reflex)-evoked contraction by up to 50% in control and 75-80% in cyclophosphamide-treated rats. Subsequent addition of PPADS further reduced the contractions. Conclusion: The micturition reflex response is increased following cyclophosphamide-induced cystitis, as compared to control. The likely cause is sensitization at mechanosensor level in the micturition arc, which overrides the decrement of the efferent cholinergic effects. © 2014 Wiley Periodicals, Inc.
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| 5. |
- Aydogdu, Özgu, 1978, et al.
(författare)
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Cross-organ sensitization between the prostate and bladder in an experimental rat model of lipopolysaccharide (LPS)-induced chronic pelvic pain syndrome.
- 2021
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Ingår i: BMC urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the current study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function via prostate-to-bladder cross-sensitization in a rat model of lipopolysaccharide (LPS)-induced prostate inflammation.Male rats were intraprostatically injected with LPS or saline, serving as control. Micturition parameters were examined in a metabolic cage 10 or 14days later. Subsequently, to evaluate bladder function, cystometry was performed. Micturition cycles were induced by saline infusion and cholinergic and purinergic contractile responses were measured by intravenous injection with methacholine and ATP, respectively. Thereafter, the prostate and bladder were excised and assessed histopathologically for possible inflammatory changes.Metabolic cage experiments showed increased urinary frequency in rats with LPS-induced CP/CPPS. Cystometry showed a significant increase in the number of non-voiding contractions, longer voiding time and lower compliance in CP/CPPS animals compared to controls. Induction of CP/CPPS led to significantly reduced cholinergic and purinergic bladder contractile responses. Histopathological analysis demonstrated prostatic inflammation in CP/CPPS animals. There were no significant differences between the groups regarding the extent or the grade of bladder inflammation. Prostate weight was not significantly different between the groups.The present study shows that prostate-to-bladder cross-sensitization can be triggered by an infectious focus in the prostate, giving rise to bladder overactivity and alterations in both afferent and efferent signalling. Future studies are required to fully understand the underlying mechanisms.
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| 8. |
- Aydogdu, Özgu, 1978, et al.
(författare)
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Prostate-to-bladder cross-sensitization in a model of zymosan-induced chronic pelvic pain syndrome in rats.
- 2021
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Ingår i: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 81:4, s. 252-260
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function and pathophysiology.To create a model for CPPS, rats were intraprostatically injected with zymosan or saline, serving as control. Metabolic cage experiments were performed 7, 14, or 21 days after zymosan injection and after 14 days in the control group. Thereafter, cystometry was performed in which simulated micturition cycles were induced by saline infusion and contractile responses to the cholinergic agonist methacholine and the purinergic agonist ATP were measured. Following cystometry, the prostate and urinary bladder were excised and assessed histopathologically for possible inflammatory changes.Metabolic cage data revealed a significantly increased urinary frequency in zymosan treated rats. Likewise, the volume per micturition was significantly lower in all CPPS groups compared to controls. Cystometry showed a significant increase in the number of nonvoiding contractions, longer voiding time, and a trend towards lower compliance in CPPS rats compared to controls. Induction of CPPS led to significantly reduced cholinergic and purinergic contractile responses. Histopathological analysis demonstrated prostatic inflammation in all CPPS groups, in particular in later stage groups. Both the extent and grade of bladder inflammation were significantly higher in CPPS groups compared to controls.The current findings demonstrate a potential prostate-to-bladder cross-sensitization leading to symptoms of bladder overactivity and signs of bladder inflammation. Future clinical studies are required to verify the outcomes of the current study and enable advancement of patient care.
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| 10. |
- Aydogdu, Özgu, 1978, et al.
(författare)
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Treatment with the soluble guanylate cyclase activator BAY 60-2770 normalizes bladder function in an in vivo rat model of chronic prostatitis.
- 2022
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Ingår i: European journal of pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 927
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60-2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS.Forty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8-20, the rats were treated with either dimethylsulphoxide (DMSO; vehicle), celecoxib, BAY 60-2770 or a combination of celecoxib and BAY 60-2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathologically.Induction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60-2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60-2770, either alone or in combination with celecoxib. The immunohistochemical analysis showed signs of prostate inflammation, but not bladder inflammation.Induction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60-2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.
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