Molecular and Morphological Characteristics of the De-Obstructed Rat Urinary Bladder—An Update

Abstract

Many patients with outlet obstruction secondary to prostatic enlargement have lower urinary tract symptoms (LUTSs) and an increased frequency of micturition. The standard treatment is transurethral resection of the prostate (TURP), which alleviates obstruction and symptoms. However, after TURP, 20–40 percent of patients continue to experience LUTSs. The aim of the present study in rats was to identify the mechanisms that do not normalize after the removal of the obstruction and that could explain the persisting symptoms. We had microarray data from control, obstructed, and de-obstructed female rat bladders, which made it possible to study 14,553 mRNA expressions. We also had a bank of electron micrographs from similar detrusors. Microarrays: There were significant differences between the control and obstructed bladders for 1111 mRNAs. The obstructed and de-obstructed bladders differed significantly for 1059 mRNAs. The controls and the de-obstructed bladders differed significantly for 798 mRNAs. We observed many mRNAs that were increased in the obstructed bladder and then decreased to control levels after de-obstruction, and many mRNAs that were decreased in the obstructed bladder and then increased following de-obstruction. mRNAs that were significantly higher or lower in the de-obstructed bladder than in the control bladder were also found. Ultrastructure: The detrusor cells in the obstructed bladders had cross-sectional areas that were much larger than those in the controls. The control cells had smooth outlines and similar cross-sectional areas. The de-obstructed detrusor cells had larger cross-sectional areas than the controls, as well as corrugated surfaces. The cell areas varied, suggesting that the shrinkage of the de-obstructed cells was not even. We did not find any points of contact of the gap junction plaque type between the detrusor cells. There were abundant finger-like processes between the detrusor cells in the obstructed and in de-obstructed bladders, which were only occasionally found in the control detrusors. They are the only possible localization for gap junction channels. The de-obstructed rat bladder is not an organ with properties intermediate between those of the control and obstructed bladders. Instead, de-obstructed bladders have gene expressions, morphologies, and functional properties of the individual cells and their organization, which make them distinctly different from both control and obstructed bladders.

Is bladder outlet obstruction rat model to induce overactive bladder (OAB) has similarity to human OAB? : Research on the events in smooth muscle, collagen, interstitial cell and telocyte expression

“…7 In our current study, we have demonstrated an increased in bladder weight, muscle hypertrophy, and the predominance collagen content in which is consistent with the ndings of other researchs. 2,14,22 Few studies demonstrated the presence of ICCs in the OAB of animal model. 15,16 In the current study we demonstrated the expression of c-kit immunoreactive interstitial cells of Cajal in the BOO rat model compared to the normal control.…”

Can Urinary Bladder Innervation Be Restored After Outlet Obstruction and Denervation?

“…These arrays have been used to characterize what happens at the molecular level during the growth of the obstructed bladder or denervated bladder and to check, in a systematic manner, the effect of obstruction and denervation for the mRNA expression of around 15,000 proteins. The microarrays have been used in other publications [ 3 , 12 , 13 ] and are publicly available (GEO accession numbers GSE47080 and 104540).…”

“…Array data show that the hypertrophic response to denervation and obstruction are quite similar. One example is that the messenger RNA (mRNA) for the gap junction protein connexin 43 increases in both (by 2.63 in 10-day obstructed bladder, and by 3.30 in 10-day denervated bladder) [ 3 ]. An increased number of connexons between the smooth muscle cells might be a compensatory mechanism counteracting the decrease or absence of motor nerve terminals.…”

“…Hindi et al [ 10 ] found e.g., a sevenfold increase in brain-derived neurotrophic factor (BDNF) mRNA in diabetic bladders but no effect by sucrose feeding. We have previously reported a 2-fold increase of BDNF mRNA in obstructed bladders [ 3 ]. BDNF stimulates sprouting of parasympathetic axons from the pelvic ganglia [ 11 ].…”

De-obstruction of bladder outlet in humans reverses organ remodelling by normalizing the expression of key transcription factors

“…Alternatively, it is possible to monitor both the functional and molecular changes in the bladder after surgical de-obstruction, and this was done in a number of animal studies, mostly in larger rodents such as rats [ 8 , 9 ], guinea pigs [ 10 ] and rabbits [ 11 ]. It was noted that despite the overall improvement of the micturition parameters, complete restoration of bladder function did not occur [ 12 ], and many molecular changes persisted after the relief of obstruction in animals [ 13 ].…”