Assessments of neurogenic bladder dysfunction induced by spinal cord injury, bladder outlet obstruction and diabetes: a comparative study of rat models

脊髓损伤、膀胱出口梗阻和糖尿病引起的神经源性膀胱功能障碍的评估:大鼠模型的比较研究

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Abstract

BACKGROUND: Neurogenic bladder (NB) refers to urinary storage and voiding dysfunction resulting from neurological disorders. Animal models of NB are commonly used in preclinical studies, but the distinct characteristics of various modeling techniques are infrequently compared. This study aimed to evaluate and compare the functional and pathological outcomes of different NB rat models. METHODS: Three rat NB models were induced by spinal cord injury (SCI), bladder outlet obstruction (BOO), and diabetes. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels, along with urine flow dynamics, were assessed at weeks 1, 2, 4, and 8. At the 10-week endpoint, animals were euthanized, and bladder weights were recorded for each specimen. Pathological analysis and western blotting were conducted to evaluate bladder muscle fibrosis. RESULTS: All three rat NB models were successfully established. At week 8, the average maximum/minimum bladder pressures for the SCI, BOO, and diabetic NB rats were 34.0/27.8, 40.4/30.2, and 32.1/28.8 mmH(2)O, respectively, while bladder capacity and residual volumes were 4.32/4.245, 5.35/5.084, and 4.20/4.048 mL, respectively. The average Scr levels were 52.2, 54.6, and 37.7 mmol/L, and BUN levels were 15.4, 13.8, and 13.9 mmol/L for the three groups. Compared to the control, bladder weights and volumes were significantly increased in the NB groups. Histopathological examination revealed marked thickening and disorganization of the muscle bundles in NB bladders, along with notable inflammatory cell infiltration within the epithelial layer. Immunohistochemical and western blot analyses showed increased fibronectin expression in the NB model bladders. CONCLUSIONS: The three NB rat models effectively replicated clinical and pathological features, including reduced bladder compliance, renal dysfunction, and bladder fibrosis. Among these models, SCI offers the fastest method for inducing NB. Renal function impairment was more pronounced in the SCI- and BOO-induced NB models, with BOO resulting in the most significant pathological changes in the bladder.

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