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J Surg Res. 2013 Aug;183(2):598-605. doi: 10.1016/j.jss.2013.02.030. Epub 2013 Mar 13.

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

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1
Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

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 Ca(2+) 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 Ca(2+) 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:

Bladder; Glivec; Interstitial cell; Sacral cord injury; Suprasacral cord injury

PMID:
23608618
DOI:
10.1016/j.jss.2013.02.030
[Indexed for MEDLINE]
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