Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity

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Abstract

Objectives: To evaluate the expression of sphingosine kinase 1 (SPK1) in the bladder wall in patients with neurogenic lower urinary tract dysfunction and its association with clinical, urodynamic and pathological features. Materials and Methods: The expression of SPK1 was studied in bladder wall specimens obtained from cystectomy using immunohistochemistry in ten patients with spinal cord injury (n=8) or multiple sclerosis (n=2) with urodynamically proven neuropathic bladder dysfunction, and in controls (n=5). Inflammation and fibrosis were analysed with histological criteria and SPK1 expression was determined by individual immunohistochemical staining. Results: Significant increased SPK1 urothelial immunoreactivity was shown in patients compared to control group (p=0.03). By contrast, SPK1 immunoreactivity in patients was significantly decreased in the sub-urothelium, muscles and nerves, p=0.02; 0.01 and 0.003, respectively. Patients with neurogenic detrusor overactivity (NDO) had higher SPK1 urothelium expression than those without any DO (p=0.04). Conclusions: SPK1 is expressed in the human bladder wall, specifically the urothelium, in bladder specimens from patients with NDO. The role of SPK1 in the pathophysiology of NDO needs further elucidation.

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Urinary bladder contraction and relaxation: physiology and pathophysiology.

Anders Arner, Karl Andersson (2004)

The detrusor smooth muscle is the main muscle component of the urinary bladder wall. Its ability to contract over a large length interval and to relax determines the bladder function during filling and micturition. These processes are regulated by several external nervous and hormonal control systems, and the detrusor contains multiple receptors and signaling pathways. Functional changes of the detrusor can be found in several clinically important conditions, e.g., lower urinary tract symptoms (LUTS) and bladder outlet obstruction. The aim of this review is to summarize and synthesize basic information and recent advances in the understanding of the properties of the detrusor smooth muscle, its contractile system, cellular signaling, membrane properties, and cellular receptors. Alterations in these systems in pathological conditions of the bladder wall are described, and some areas for future research are suggested.

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Histologic features in the urinary bladder wall affected from neurogenic overactivity--a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A.

Bruce Reitz, Pierre Denys, Eva Comperat … (2006)

To study histological features and morphological differences in bladder wall specimen from patients with and without botulinum toxin A injections and to compare those issues in responders and non-responders to the toxin therapy. Bladder wall specimen obtained from cystectomy in 45 patients with neurogenic overactive bladders with and without injection of botulinum toxin A into the detrusor muscle for treatment of neurogenic incontinence were evaluated concerning the histological criteria inflammation, oedema and fibrosis of the bladder wall. Bladder wall specimen obtained from patients suffering from neurogenic detrusor overactivity showed important histological alterations. Generally, inflammatory infiltration, oedema and fibrosis of the bladder wall were frequently observed. When comparing specimen from patients who had received botulinum toxin injection to those from patients who had not, there was no difference concerning inflammation and oedema. However, patients who had received botulinum toxin injection showed significantly less fibrosis of the bladder wall than those who had not received the toxin injection (p<0.00073). When comparing specimen from responders and non-responders to the botulinum toxin therapy, there was no difference in inflammation. Although not significant, a trend was observed that responder to the toxin therapy had less fibrosis and oedema of the bladder wall than non-responder. In our study injection of botulinum toxin into the detrusor muscle did not lead to increased fibrotic activity within the bladder wall, on the contrary patients with previous botulinum toxin injection revealed significant less fibrosis than patients without toxin injection.

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Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity.

R. Popat, Vinay Kalsi, Sohier Elneil … (2008)

We examined, for the first time in a prospective study, the histological changes in the urothelium and suburothelium of patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat treatments with intradetrusor BoNTA. Flexible cystoscopic bladder biopsies were obtained from patients with urodynamically proven intractable spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis, hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical comparisons were significant at p values less than 0.05. Signs of chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs. 50% of IDO, p=0.049), 67.6% of post-first biopsies and 86.4% after repeat injections. The two groups were comparable for degree of baseline inflammation, which did not change significantly after first injection and up to 16 wk after a third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally before and after treatment, but not after repeat injections. No dysplasia or hyperplasia was identified. Eosinophils were identified more frequently in biopsies taken after repeat injections compared with the post-first injection and baseline biopsies (chi2=8.23, p=0.018). No difference existed between NDO and IDO bladders. BoNTA injections do not appear to be producing significant inflammatory changes, fibrosis, or dysplastic changes in human bladder urothelium/suburothelium after a single injection and in a limited number of repeat treatment biopsies. The presence of eosinophils might be treatment-related, because they were mostly found in post-treatment biopsies.

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SciELO Brazil ID:: S1677-55382015000601141

DOI:: 10.1590/S1677-5538.IBJU.2014.0676

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http://creativecommons.org/licenses/by/4.0/

ScienceOpen disciplines: Urology

Keywords: Urinary Bladder, Neurogenic,Urinary Bladder, Overactive,sphingosine kinase [Supplementary Concept],Urothelium,Immunochemistry

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ScienceOpen disciplines: Urology

Keywords: Urinary Bladder, Neurogenic, Urinary Bladder, Overactive, sphingosine kinase [Supplementary Concept], Urothelium, Immunochemistry

Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity

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UCL: UN SDG 01 No Poverty

Most cited references 20

Urinary bladder contraction and relaxation: physiology and pathophysiology.

Histologic features in the urinary bladder wall affected from neurogenic overactivity--a comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A.

Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity.

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