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The effects of Glivec on the urinary bladder excitation of rats with suprasacral or sacral spinal cord transection

Published:March 13, 2013DOI:https://doi.org/10.1016/j.jss.2013.02.030

      Abstract

      Background

      To investigate the effects of the c-kit blocker imatinib mesylate (Glivec) on the bladders of animals with suprasacral cord injury (SSCI) and sacral cord injury (SCI).

      Materials and methods

      We randomized 60 female Sprague-Dawley rats into control, sham, SSCI (T8/9 transection), and SCI (S1-3 transection) groups. Six weeks later, we evaluated the effects of stepwise Glivec administrations on urinary bladder contraction using cystometry and the detrusor strip stretch-test. We investigated spontaneous calcium transients of kit-positive interstitial cells of Cajal (ICCs) with the preloaded Ca2+ indicator fluo-3AM. The expression levels of c-kit and the number of ICCs in those bladders were determined using Western blot and fluorescence staining analyses, respectively.

      Results

      Bladder capacity and compliance were decreased in SSCI bladders and increased in SCI bladders (P < 0.05). The amplitude and frequency of spontaneous contractions of detrusor strips, the frequency and relative fluorescence intensity of the spontaneous Ca2+ waves, and c-kit expression in the bladder were significantly increased in the SSCI group and decreased in the SCI group compared with the control and sham groups (P < 0.05). The dose-dependent effects of Glivec also confirmed consistent functional variations in bladder activity.

      Conclusions

      The expressions and effects of Glivec were enhanced in SSCI bladders and inhibited in SCI bladders, which may indicate potential roles of ICCs for the c-kit signaling pathway in the pathogenesis of SSCI and SCI bladder.

      Keywords

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      References

        • Kwon B.K.
        • Oxland T.R.
        • Tetzlaff W.
        Animal models used in spinal cord regeneration research.
        Spine (Phila Pa 1976). 2002; 27: 1504
        • Cruz C.D.
        • Cruz F.
        Spinal cord injury and bladder dysfunction: new ideas about an old problem.
        ScientificWorldJournal. 2011; 11: 214
        • Davidson R.A.
        • McCloskey K.D.
        Morphology and localization of interstitial cells in the guinea pig bladder: structural relationships with smooth muscle and neurons.
        J Urol. 2005; 173: 1385
        • McCloskey K.D.
        • Gurney A.M.
        Kit positive cells in the guinea pig bladder.
        J Urol. 2002; 168: 832
        • Shafik A.
        • El-Sibai O.
        • Shafik A.A.
        • Shafik I.
        Identification of interstitial cells of Cajal in human urinary bladder: concept of vesical pacemaker.
        Urology. 2004; 64: 809
        • McCloskey K.D.
        • Anderson U.A.
        • Davidson R.A.
        • Bayguinov Y.R.
        • Sanders K.M.
        • Ward S.M.
        Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice.
        Br J Pharmacol. 2009; 156: 273
        • Anderson U.A.
        • Carson C.
        • McCloskey K.D.
        KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder.
        J Urol. 2009; 182: 330
        • Hashitani H.
        • Yanai Y.
        • Suzuki H.
        Role of interstitial cells and gap junctions in the transmission of spontaneous Ca2+ signals in detrusor smooth muscles of the guinea-pig urinary bladder.
        J Physiol. 2004; 559: 567
        • Johnston L.
        • Woolsey S.
        • Cunningham R.M.
        • et al.
        Morphological expression of KIT positive interstitial cells of Cajal in human bladder.
        J Urol. 2010; 184: 370
        • McCloskey K.D.
        Interstitial cells in the urinary bladder—localization and function.
        Neurourol Urodyn. 2010; 29: 82
        • Kubota Y.
        • Hashitani H.
        • Shirasawa N.
        • et al.
        Altered distribution of interstitial cells in the guinea pig bladder following bladder outlet obstruction.
        Neurourol Urodyn. 2008; 27: 330
        • Chen W.
        • Jiang C.
        • Jin X.
        • Shen W.
        • Song B.
        • Li L.
        Roles of stem cell factor on loss of interstitial cells of Cajal in bladder of diabetic rats.
        Urology. 2011; 78: 1443.e1
        • Kubota Y.
        • Biers S.M.
        • Kohri K.
        • Brading A.F.
        Effects of imatinib mesylate (Imatinib mesylate) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder.
        Neurourol Urodyn. 2006; 25: 205
        • Biers S.M.
        • Reynard J.M.
        • Doore T.
        • Brading A.F.
        The functional effects of a c-kit tyrosine inhibitor on guinea-pig and human detrusor.
        BJU Int. 2006; 97: 612
        • So K.Y.
        • Kim S.H.
        • Sohn H.M.
        • et al.
        Carbachol regulates pacemaker activities in cultured interstitial cells of Cajal from the mouse small intestine.
        Mol Cells. 2009; 27: 525
        • Vizzard M.A.
        Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction.
        Exp Neurol. 2000; 161: 273
        • Toosi K.K.
        • Nagatomi J.
        • Chancellor M.B.
        • Sacks M.S.
        The effects of long-term spinal cord injury on mechanical properties of the rat urinary bladder.
        Ann Biomed Eng. 2008; 36: 1470
        • Nagatomi J.
        • Toosi K.K.
        • Grashow J.S.
        • Chancellor M.B.
        • Sacks M.S.
        Quantification of bladder smooth muscle orientation in normal and spinal cord injured rats.
        Ann Biomed Eng. 2005; 33: 1078
        • Sui G.P.
        • Rothery S.
        • Dupont E.
        • Fry C.H.
        • Severs N.J.
        Gap junctions and connexin expression in human suburothelial interstitial cells.
        BJU Int. 2002; 90: 118
        • Wu C.
        • Sui G.P.
        • Fry C.H.
        Purinergic regulation of guinea pig suburothelial myofibroblasts.
        J Physiol. 2004; 559: 231
        • Sui G.P.
        • Wu C.
        • Roosen A.
        • Ikeda Y.
        • Kanai A.J.
        • Fry C.H.
        Modulation of bladder myofibroblast activity: implications for bladder function.
        Am J Physiol Renal Physiol. 2008; 295: F688
        • Lin L.
        • Xu L.M.
        • Zhang W.
        • et al.
        Roles of stem cell factor on the depletion of interstitial cells of Cajal in the colon of diabetic mice.
        Am J Physiol Gastrointest Liver Physiol. 2010; 298: G241
        • Seki S.
        • Sasaki K.
        • Fraser M.O.
        • et al.
        Immunoneutralization of nerve growth factor in lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats.
        J Urol. 2002; 168: 2269
        • Shea V.K.
        • Cai R.
        • Crepps B.
        • Mason J.L.
        • Perl E.R.
        Sensory fibers of the pelvic nerve innervating the Rat's urinary bladder.
        J Neurophysiol. 2000; 84: 1924
        • Zagorodnyuk V.P.
        • Gibbins I.L.
        • Costa M.
        • Brookes S.J.
        • Gregory S.J.
        Properties of the major classes of mechanoreceptors in the guinea pig bladder.
        J Physiol. 2007; 585: 147