Acute and late radiation damage in mouse bladder: A comparison of urination frequency and cystometry

Stewart, F. A.; Lundbeck, Finn; Oussoren, Y.; Luts, A.

doi:10.1016/0360-3016(91)90278-c

Cited by 34 publications

(24 citation statements)

References 20 publications

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“…25 The first phase is the acute damage consisting of urothelial swelling, ulceration, and vascular endothelial cell damage. 26,27 The second phase is the infiltration of inflammatory cells. [26][27][28] The third phase is chronic and is associated with collagen deposition and developing fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 The second phase is the infiltration of inflammatory cells. [26][27][28] The third phase is chronic and is associated with collagen deposition and developing fibrosis. 26,27,29 Some studies reported that animal urinary bladder damage induced by a single dose of radiation had pathological changes that included epithelial denudation and focal hyperplasia with ulceration, 26 changes in axon profiles and mast cell density, 27 and increased formation of superoxide free radicals.…”

Section: Discussionmentioning

confidence: 99%

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Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

Imamura

Ishizuka

Zhang

et al. 2012

Tissue Engineering Part A

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The purpose of this study was to determine whether bone marrow-derived cells implanted into radiation-injured urinary bladders could reconstruct functional bladder tissues. The pelvic region of anesthetized female SpragueDawley (SD) rats was irradiated with 2 Gy once a week for 5 weeks. After the last irradiation, the rats were maintained for 2 weeks. Bone marrow cells were harvested from the femurs of donor male green fluorescence protein (GFP)-transfected SD rats and cultured for 7 days. Two weeks after the last radiation exposure, the cultured adherent, proliferating bone marrow-derived cells were implanted into the walls of irradiated urinary bladders. For controls, cell-free solutions were similarly injected. Four weeks after donor cell or control implantations, cystometric, histological, and immunohistochemical investigations were performed. Two weeks after the last irradiation, the smooth muscle layers and nerve fibers of the irradiated urinary bladders were disorganized. The proportions of smooth muscle layer and nerve fiber areas were significantly decreased compared with sham-irradiated urinary bladders. In addition, the remaining smooth muscle cells within the irradiated urinary bladders expressed P4HB, an indicator of collagen synthesis. In the cystometric investigations, the voiding interval of irradiated rats was irregularly prolonged, 7.92 -1.09 min, and the residual volume, 0.13 -0.03 mL, was significantly higher compared with the sham-irradiated rats (5.50 -0.43 mL and 0.05 -0.01 mL). After 4 weeks, the smooth muscle layers and nerve fibers in the cell-free control urinary bladders remained similar to the preimplanted irradiated urinary bladders; however, the cell-implanted urinary bladders contained reconstructed smooth muscle layers and nerve fibers, the proportions of each were significantly higher than those in the cell-free injected controls. The expression of P4HB within the cell-implanted urinary bladders decreased. Some GFPpositive implanted cells differentiated into smooth muscle-and nerve-like cells and became organized into the reconstructed tissues. The voiding interval of the cell-implanted rats, 5.46 -0.33 min, was regular and similar to that of the sham-irradiated rats, and significantly less than that of the cell-free injected controls, 7.39 -0.54 min. The residual volume, 0.04 -0.01 mL, was similar to that of the sham-irradiated rats and significantly decreased compared with that of the cell-free injected controls, 0.15 -0.05 mL. Therefore, the implantation of bone marrowderived cells is a potentially useful treatment for radiotherapy-induced urinary dysfunctions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

Imamura

Ishizuka

Zhang

et al. 2012

Tissue Engineering Part A

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“…However, the total allowable radiation dose is limited by the potential for developing irradiation-induced cystitis (35). Pathologically, irradiation damage to the bladder occurs in three distinct phases (36). Acute damage after a single dose consists of urothelial swelling, ulceration, and vascular endothelial cell damage.…”

mentioning

confidence: 99%

“…A subacute phase occurs within 4-6 days of radiotherapy, with infiltration of inflammatory cells (30). A third chronic phase is associated with collagen deposition and fibrosis, leading to a decrease in bladder compliance (30,36). Clinically, the long-term side effects of radiation therapy include decreased bladder volume and increased frequency, urgency, and dysuria (7,25).…”

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confidence: 99%

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Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis

Kanai¹,

Zeidel²,

Lavelle³

et al. 2002

American Journal of Physiology-Renal Physiology

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Urinary bladder cystitis occurs in patients receiving radiation therapy for pelvic tumors. Radiation-induced formation of superoxide radicals is believed to damage the urothelium, exposing the underlying bladder smooth muscle to urine, culminating in nerve irritation and muscle dysfunction. We tested whether overexpression of MnSOD could decrease superoxide levels and protect the bladder from radiation damage. Pelvic irradiation led to sloughing of urothelial umbrella cells, with decreased transepithelial resistance, increased water and urea permeabilities, and increased expression of inducible nitric oxide synthase. Six months after irradiation, cystometrograms showed elevated intravesical pressures and prolonged voiding patterns. However, urothelia transfected with the MnSOD transgene recovered from radiation injury more rapidly, and detrusor function was much closer to that of control bladders than irradiated bladders without the transgene. We conclude that MnSOD gene therapy is protective, which could lead to its use in mitigating radiation cystitis and preventing dysfunction of the urinary bladder.

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Influence of animal husbandry practices on void spot assay outcomes in C57BL/6J male mice

Keil

Abler

Altmann

et al. 2014

Neurourol. Urodynam.

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Aims Mice are increasingly being used as models to investigate aspects of urinary dysfunction that humans with lower urinary tract symptoms (LUTS) experience. One method used to examine voiding function is the spontaneous void spot assay. The purpose of this study was to characterize and identify animal husbandry conditions that might confound results of the spontaneous void spot assay in male C57Bl/6J mice. Methods Mice were placed in cages lined with filter paper for four hours and urine was visualized with UV transillumination. Voiding parameters including urine spot number, spot size, total urine area, primary void area, corner and center voiding were quantified. Results Adult male mice void more frequently with advancing age and a subpopulation (5–10%) display a frequent spotting pattern at 6–9 weeks of age. Voiding was not significantly different in male mice weaned to group housing (4–6 per cage) versus single housing, and was not altered when they were used as breeders. Voiding was changed upon transferring group housed adult males to single density cages, which decreased total urine area. Repeated assays of male voiding behavior over three consecutive days increased primary void area by the third day of monitoring and revealed that voiding behavior is impacted by routine cage changes and time of day. Conclusions Together these results identify housing and husbandry practices that influence male voiding behaviors in the spontaneous void spot assay and will inform voiding behavior analyses conducted with male C57Bl/6J mice.

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Acute and late radiation damage in mouse bladder: A comparison of urination frequency and cystometry

Cited by 34 publications

References 20 publications

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

Bone Marrow-Derived Cells Implanted into Radiation-Injured Urinary Bladders Reconstruct Functional Bladder Tissues in Rats

Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis

Influence of animal husbandry practices on void spot assay outcomes in C57BL/6J male mice

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