Division of Urology, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Glenolden, Pennsylvania;
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and.
Am J Physiol Renal Physiol. 2014 Sep 1;307(5):F612-22. doi: 10.1152/ajprenal.00151.2014. Epub 2014 Jul 9.
In the present study, we aimed to determine whether mice with coronavirus-induced encephalomyelitis (CIE) develop neurogenic bladder dysfunction that is comparable with the neurogenic detrusor overactivity observed in patients with multiple sclerosis. Adult mice (C57BL/6J, 8 wk of age, n = 146) were inoculated with a neurotropic strain of mouse hepatitis virus (A59 strain) and followed for 4 wk. Inoculation with the virus caused a significant neural deficit in mice with an average clinical symptom score of 2.6 ± 0.5 at 2 wk. These changes were accompanied by 25 ± 5% weight loss at 1 and 2 wk postinoculation (P ≤ 0.001 vs. baseline) followed by a recovery phase. Histological analysis of spinal cord sections revealed multifocal sites of demyelinated lesions. Assessment of micturition patterns by filter paper assay determined an increase in the number of small and large urine spots in CIE mice starting from the second week after inoculation. Cystometric recordings in unrestrained awake animals confirmed neurogenic bladder overactivity at 4 wk postinoculation. One week after inoculation with the A59 strain of mouse hepatitis virus, mice became increasingly sensitive to von Frey filament testing with responses enhanced by 45% (n = 8, P ≤ 0.05 vs. baseline at 4 g); however, this initial increase in sensitivity was followed by gradual and significant diminution of abdominal sensitivity to mechanical stimulation by 4 wk postinoculation. Our results provide direct evidence showing that coronavirus-induced demyelination of the central nervous system causes the development of a neurogenic bladder that is comparable with neurogenic detrusor overactivity observed in patients with multiple sclerosis.
在本研究中，我们旨在确定是否患有冠状病毒诱导的脑脊髓炎 (CIE) 的小鼠会出现神经原性膀胱功能障碍，这种障碍与多发性硬化症患者中观察到的神经原性逼尿肌过度活动相当。成年小鼠（C57BL/6J，8 周龄，n=146）接种了神经亲和性鼠肝炎病毒（A59 株），并随访了 4 周。病毒接种导致小鼠出现明显的神经缺陷，2 周时平均临床症状评分为 2.6±0.5。这些变化伴随着 1 和 2 周接种后 25±5%的体重减轻（P≤0.001 与基线相比），随后进入恢复阶段。脊髓切片的组织学分析显示脱髓鞘病变的多灶性部位。滤纸检测评估排尿模式，发现从接种后第 2 周开始，CIE 小鼠的小和大尿斑数量增加。在不受约束的清醒动物中进行的膀胱测压记录证实，在接种后 4 周时出现神经原性膀胱过度活动。在接种 A59 株鼠肝炎病毒后 1 周，小鼠对冯弗雷尔细丝检测的敏感性逐渐增加，反应增强了 45%（n=8，P≤0.05 与 4 g 时的基线相比）；然而，这种最初的敏感性增加随后被接种后 4 周时对机械刺激的腹部敏感性逐渐显著降低所取代。我们的结果提供了直接证据，表明冠状病毒诱导的中枢神经系统脱髓鞘导致神经原性膀胱的发展，这种膀胱与多发性硬化症患者中观察到的神经原性逼尿肌过度活动相当。
