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用于评估食蟹猴创伤性脊髓损伤药物治疗的模型()

Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques ().

作者信息

Seth Nitin, Simmons Heather A, Masood Farah, Graham William A, Rosene Douglas L, Westmoreland Susan V, Cummings Sheila M, Gwardjan Basia, Sejdic Ervin, Hoggatt Amber F, Schalk Dane R, Abdullah Hussein A, Sledge John B, Nesathurai Shanker

机构信息

School of Engineering, University of Guelph, Guelph, Ontario, Canada.

Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin.

出版信息

Comp Med. 2018 Feb 1;68(1):63-73.

Abstract

Here we present the results of experiments involving cynomolgus macaques, in which a model of traumatic spinal cord injury (TSCI) was created by using a balloon catheter inserted into the epidural space. Prior to the creation of the lesion, we inserted an EMG recording device to facilitate measurement of tail movement and muscle activity before and after TSCI. This model is unique in that the impairment is limited to the tail: the subjects do not experience limb weakness, bladder impairment, or bowel dysfunction. In addition, 4 of the 6 subjects received a combination treatment comprising thyrotropin releasing hormone, selenium, and vitamin E after induction of experimental TSCI. The subjects tolerated the implantation of the recording device and did not experience adverse effects due the medications administered. The EMG data were transformed into a metric of volitional tail moment, which appeared to be valid measure of initial impairment and subsequent natural or treatment-related recovery. The histopathologic assessment demonstrated widespread axon loss at the site of injury and areas cephalad and caudad. Histopathology revealed evidence of continuing inflammation, with macrophage activation. The EMG data did not demonstrate evidence of a statistically significant treatment effect.

摘要

在此,我们展示了涉及食蟹猴的实验结果,其中通过将球囊导管插入硬膜外腔创建了创伤性脊髓损伤(TSCI)模型。在造成损伤之前,我们插入了肌电图记录设备,以便于测量TSCI前后的尾巴运动和肌肉活动。该模型的独特之处在于损伤仅限于尾巴:实验对象没有出现肢体无力、膀胱损伤或肠道功能障碍。此外,6只实验对象中有4只在实验性TSCI诱导后接受了促甲状腺激素释放激素、硒和维生素E的联合治疗。实验对象耐受了记录设备的植入,并且没有因所施用的药物而出现不良反应。肌电图数据被转换为意志性尾巴力矩指标,这似乎是初始损伤以及随后自然恢复或与治疗相关恢复的有效度量。组织病理学评估显示,损伤部位以及头侧和尾侧区域存在广泛的轴突损失。组织病理学显示有持续炎症的迹象,伴有巨噬细胞激活。肌电图数据未显示出具有统计学意义的治疗效果的证据。

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