International Collaboration on Repair Discoveries (ICORD), Departments of Department of Orthopaedics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Neuroscience, Department of Orthopaedics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
J Neurotrauma. 2021 May 1;38(9):1306-1326. doi: 10.1089/neu.2020.7404. Epub 2021 Mar 2.
There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.
现在越来越需要开发一些方法,不仅能改善脊髓损伤(SCI)后神经原性下尿路功能障碍(NLUTD)的临床管理,还能推进旨在恢复膀胱功能的治疗干预措施。尽管临床前研究经常使用啮齿动物 SCI 模型,但猪等大型动物可能在促进设备或治疗方法的开发方面发挥重要的转化作用。因此,本研究的目的是开发一种尿动力学方案,以描述 SCI 猪模型中的 NLUTD。开发用于对雌性尤卡坦小型猪进行尿动力学研究的方案的迭代过程始于一组脊髓完整的麻醉猪。随后,在 T2 或 T9-T11 脊髓水平进行挫伤-压迫性 SCI 前后,对一组清醒、轻度约束的猪进行了尿动力学研究。研究结束时,从膀胱组织中获得组织学分析样本。所有麻醉猪的膀胱都没有收缩能力,一旦达到容量就会出现溢出性失禁。未受伤的清醒猪在排尿阶段表现出适当的外尿道括约肌松弛和收缩。SCI 猪表现出神经原性逼尿肌过度活动和显著升高的排尿后残余尿量。与对照组相比,SCI 组的膀胱更重、更厚。开发的尿动力学方案允许在 SCI 后不同时间点对猪的下尿路功能进行重复评估。该技术显示了将猪作为中间大型动物模型用于 NLUTD 转化研究的潜力。