Irreversible Bladder Remodeling Induced by Fibrosis

Kim, Su Jin; Kim, Jayoung; Na, Yong Gil; Kim, Khae Hawn

doi:10.5213/inj.2142174.087

Cited by 21 publications

(18 citation statements)

References 43 publications

(47 reference statements)

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“…A significant increase in the bladder wall and urothelial thickness were seen in SCI rats. These findings are consistent with previous clinical observations that hypothesized that SCI and the resulting lack of trophic action on the urothelium might lead to a cascade of events involving urothelial proliferation, differentiation, and apoptosis [29][30][31]. Mucosal denervation, cell adhesion molecules, secretory immunoglobulin (IgA), growth factors, nitric oxide synthase (NOS), and cytokines could play a complex and interactive role in the development of the denervation-induced changes in urothelial structure and function; these cellular changes could eventually lead to increased susceptibility of the vesical urothelium to urinary tract infection, and the present animal model may be a suitable subject to determine the mechanisms.…”

Section: Discussionsupporting

confidence: 92%

A Rodent Lumbosacral Spinal Cord Injury Model Reflecting Neurological and Urological Deficits of Humans

2022

Journal of Experimental Neurology

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Spinal cord injury (SCI) to the terminal segments of the spinal cord causes severe disruption of the neural circuitry of the bladder, resulting in neurogenic underactive bladder (nUAB). We developed a rodent lumbosacral injury model to investigate the effects of bladder function and structure. A severe contusion SCI was performed over the L5-S2 segmental spinal cord (T13/L1 junction, L1 vertebra, L1/L2 junction). The injured spinal cords were scanned by advanced micro-CT imaging. Bladder function was assessed in awake rats before and at 2, 4, 6, and 8 weeks after SCI. Locomotor function was assessed using the BBB Open Field Rating Scale and the Catwalk system. Specific histological staining assessed structural bladder remodelling in control and SCI rats. Contusion SCI at the three respective segmental heights revealed variations in lesion sizes and white and gray matter sparing. However, this did not influence SCI rats' bladder and locomotor outcomes, whereas the functional deficits were comparable in control and SCI rats. From week 2 onwards, the main functional changes of nUAB in SCI rats were noticeable: a low detrusor strength with a combination of slow maximal flow rate and low leakage volumes with no to incomplete voiding. Histological analyses of bladder tissue underlined the functional outcomes by depicting a thickened bladder wall with ongoing fibrotic and uroepithelial changes. As expected, only mild locomotor impairments were determined. This model of lumbosacral SCI reproduces nUAB with structural and functional outcomes similar to human nUAB, giving future studies a well-defined framework to test therapies for nUAB conditions in a standardized rat model.

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Section: Discussionsupporting

confidence: 92%

A Rodent Lumbosacral Spinal Cord Injury Model Reflecting Neurological and Urological Deficits of Humans

2022

Journal of Experimental Neurology

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“…Due to the lack of collagen in the lamina propria, Osr1 +/− pups likely have a weak atonic bladder that is unable to empty [2].This would put a mechanical burden on the smooth muscle layer, similar to what is seen with functional bladder obstruction. Bladder obstruction has been shown to result in dysregulation of fibroblasts, and loss of ECM modulatory proteins such as MMPs, which results in collagen accumulation [30]. Once collagen accumulates, bladder function is perturbed, resulting in decreased bladder capacity and increased voiding frequency, as seen in adult Osr1 +/− mice.…”

Section: Discussionmentioning

confidence: 99%

Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder

Murugapoopathy

Cammisotto

Mossa

et al. 2021

IJMS

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The extracellular matrix of the bladder consists mostly of type I and III collagen, which are required during loading. During bladder injury, there is an accumulation of collagen that impairs bladder function. Little is known about the genes that regulate production of collagens in the bladder. We demonstrate that the transcription factor Odd-skipped related 1 (Osr1) is expressed in the bladder mesenchyme and epithelium at the onset of development. As development proceeds, Osr1 is mainly expressed in mesenchymal progenitors and their derivatives. We hypothesized that Osr1 regulates mesenchymal cell differentiation and production of collagens in the bladder. To test this hypothesis, we examined newborn and adult mice heterozygous for Osr1, Osr1+/−. The bladders of newborn Osr1+/− mice had a decrease in collagen I by western blot analysis and a global decrease in collagens using Sirius red staining. There was also a decrease in the cellularity of the lamina propria, where most collagen is synthesized. This was not due to decreased proliferation or increased apoptosis in this cell population. Surprisingly, the bladders of adult Osr1+/− mice had an increase in collagen that was associated with abnormal bladder function; they also had a decrease in bladder capacity and voided more frequently. The results suggest that Osr1 is important for the differentiation of mesenchymal cells that give rise to collagen-producing cells.

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“…Chronic BOO leads to physical changes to the detrusor smooth muscle in humans and in rabbit models to overcome the in-creased resistance during micturition [15][16][17]. However, it is not clear why a subset of men with BOO experience persistent LUTS after surgical intervention [3,4].…”

Section: Discussionmentioning

confidence: 99%

White Matter Integrity in Men With Benign Prostatic Hyperplasia and Bladder Outlet Obstruction and Its Contribution to Lower Urinary Tract Symptoms

et al. 2022

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Purpose: Lower urinary tract symptoms (LUTS) associated with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) can negatively impact quality of life. We evaluated the structural connectivity of the brain in men with BPH with chronic BOO using diffusion tensor imaging (DTI).Methods: Ambulatory male patients aged ≥45 years with BPH and BOO were recruited. LUTS was defined as an International Prostate Symptom Score (IPSS) ≥12 and a maximum urinary flow rate ≤15 mL/sec. Upon recruitment, uroflowmetry and validated questionnaires regarding bladder status were collected. DTI images from each subject were aligned with the ICBM-DTI-81 atlas, defining 50 white matter tracts (WMTs). The mean values of DTI parameters—fractional anisotropy and mean diffusivity—for each WMT were extracted. These measures were then utilized to compute Pearson correlation coefficients with clinical parameters. Objective clinical parameters included uroflowmetry parameters, postvoid residual (PVR) volume, and bladder capacity. Subjective clinical parameters were assessed using validated questionnaires: the IPSS, Incontinence Symptom Index, and Sexual Health Inventory for Men.Results: The correlation analysis revealed 15 WMTs that showed statistically significant associations (P<0.05) with objective and subjective clinical parameters. Eight tracts were associated with uroflowmetry parameters: maximum flow rate (Qmax), mean flow rate (Qmean), and PVR. Among these tracts, the middle cerebellar peduncles and left medial lemniscus were associated with Qmax; the genu of the corpus callosum, left superior corona radiata, corticospinal tract, right medial lemniscus, posterior corona radiata with Qmean; and the left posterior corona radiata with PVR. Seven tracts also demonstrated significant associations with the IPSS.Conclusions: Our results suggest correlations between the preserved white matter integrity of specific WMTs and the severity of LUTS based on objective and subjective clinical parameters, leading us to believe that a distinct pathology of the central nervous system might exist.

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Irreversible Bladder Remodeling Induced by Fibrosis

Cited by 21 publications

References 43 publications

A Rodent Lumbosacral Spinal Cord Injury Model Reflecting Neurological and Urological Deficits of Humans

A Rodent Lumbosacral Spinal Cord Injury Model Reflecting Neurological and Urological Deficits of Humans

Osr1 Is Required for Mesenchymal Derivatives That Produce Collagen in the Bladder

White Matter Integrity in Men With Benign Prostatic Hyperplasia and Bladder Outlet Obstruction and Its Contribution to Lower Urinary Tract Symptoms

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