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一种新型啮齿动物急性冲击-压缩性腰椎脊髓损伤模型

A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent.

作者信息

Moonen Gray, Satkunendrarajah Kajana, Wilcox Jared T, Badner Anna, Mothe Andrea, Foltz Warren, Fehlings Michael G, Tator Charles H

机构信息

1 Institute of Medical Science, Faculty of Medicine, University of Toronto , Toronto, Ontario, Canada .

2 Division of Genetics and Development, Toronto Western Research Institute, University Health Network , Toronto, Ontario, Canada .

出版信息

J Neurotrauma. 2016 Feb 1;33(3):278-89. doi: 10.1089/neu.2015.3937. Epub 2015 Dec 1.

Abstract

Traumatic injury to the lumbar spinal cord results in complex central and peripheral nervous tissue damage causing significant neurobehavioral deficits and personal/social adversity. Although lumbar cord injuries are common in humans, there are few clinically relevant models of lumbar spinal cord injury (SCI). This article describes a novel lumbar SCI model in the rat. The effects of moderate (20 g), moderate-to-severe (26 g) and severe (35 g, and 56 g) clip impact-compression injuries at the lumbar spinal cord level L1-L2 (vertebral level T11-T12) were assessed using several neurobehavioral, neuroanatomical, and electrophysiological outcome measures. Lesions were generated after meticulous anatomical landmarking using microCT, followed by laminectomy and extradural inclusion of central and radicular elements to generate a traumatic SCI. Clinically relevant outcomes, such as MR and ultrasound imaging, were paired with robust morphometry. Analysis of the lesional tissue demonstrated that pronounced tissue loss and cavitation occur throughout the acute to chronic phases of injury. Behavioral testing revealed significant deficits in locomotion, with no evidence of hindlimb weight-bearing or hindlimb-forelimb coordination in any injured group. Evaluation of sensory outcomes revealed highly pathological alterations including mechanical allodynia and thermal hyperalgesia indicated by increasing avoidance responses and decreasing latency in the tail-flick test. Deficits in spinal tracts were confirmed by electrophysiology showing increased latency and decreased amplitude of both sensory and motor evoked potentials (SEP/MEP), and increased plantar H-reflex indicating an increase in motor neuron excitability. This is a comprehensive lumbar SCI model and should be useful for evaluation of translationally oriented pre-clinical therapies.

摘要

腰椎脊髓创伤性损伤会导致复杂的中枢和周围神经组织损伤,引起严重的神经行为缺陷以及个人/社会方面的不利影响。尽管腰椎脊髓损伤在人类中很常见,但临床上相关的腰椎脊髓损伤(SCI)模型却很少。本文描述了一种新型大鼠腰椎SCI模型。使用多种神经行为、神经解剖学和电生理结果测量方法,评估了在腰椎脊髓L1-L2水平(椎体水平T11-T12)施加的中度(20 g)、中度至重度(26 g)和重度(35 g和56 g)夹捏冲击压缩损伤的影响。在使用微型CT进行细致的解剖定位后产生损伤,随后进行椎板切除术,并在硬膜外纳入中央和神经根成分以造成创伤性SCI。将诸如磁共振成像(MR)和超声成像等临床相关结果与强大的形态测量学相结合。对损伤组织的分析表明,在损伤的急性到慢性阶段都会出现明显的组织损失和空洞形成。行为测试显示运动功能存在显著缺陷,任何损伤组均未出现后肢负重或后肢-前肢协调的迹象。感觉结果评估显示出高度病理性改变,包括机械性异常性疼痛和热痛觉过敏,甩尾试验中回避反应增加和潜伏期缩短表明了这一点。电生理学证实了脊髓束的缺陷,表现为感觉和运动诱发电位(SEP/MEP)的潜伏期延长和波幅降低,以及足底H反射增加,表明运动神经元兴奋性增加。这是一个全面的腰椎SCI模型,应该有助于评估面向转化的临床前治疗方法。

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