Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.
Thoracic 9 Spinal Transection-Induced Model of Muscle Spasticity in the Rat: A Systematic Electrophysiological and Histopathological Characterization.
复制标题
DOI：
10.1371/journal.pone.0144642
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Marsala M
中科院分区：
文献类型：
--
作者：
Corleto JA;Bravo-Hernández M;Kamizato K;Kakinohana O;Santucci C;Navarro MR;Platoshyn O;Cizkova D;Lukacova N;Taylor J;Marsala M
作为痉挛综合征一部分的脊髓反射亢进是与慢性脊柱创伤性损伤 (SCI) 相关的主要并发症之一。导致肌肉痉挛进行性出现的主要机制是多模式的，可能包括下降抑制张力的丧失、节段性中间神经元介导的抑制的改变和/或感觉输入的反射活动增加。在这里，我们描述了 Sprague-Dawley (SD) 大鼠肌肉痉挛的慢性胸部 (Th 9) 完全横断模型。异氟烷麻醉的大鼠接受 Th9 椎板切除术，并使用手术刀片横切脊髓。横断后，量化为拉伸和皮肤反射亢进的肌肉痉挛的存在被识别并量化为以下方面的时间依赖性变化：i）踝关节旋转诱发的外周肌肉阻力（PMR）和相应的肌电图（EMG）活动，ii）霍夫曼反射，以及iii）损伤后长达8个月的爪子触觉刺激后腓肠肌的肌电图反应。为了验证该模型的临床相关性，还测试了使用临床建立的抗痉挛药物巴氯芬（GABAB受体激动剂）、替扎尼定（α2-肾上腺素能激动剂）和NGX424（AMPA受体拮抗剂）进行全身治疗后的治疗效力。在脊柱横断后的前 3 个月内，持续测量到踝关节旋转引起的肌肉阻力、霍夫曼反射幅度以及对周围施加的触觉刺激的肌电图反应的逐渐增加。这些表明痉挛综合征的变化在受伤后长达 8 个月内保持相对稳定。巴氯芬、替扎尼定和 NGX424 的全身治疗可显着但短暂地抑制脊髓反射亢进。这些数据表明，成年 SD 大鼠的慢性 Th9 脊柱横断模型代表了一个可靠的实验平台，可用于研究慢性脊柱损伤引起的痉挛的病理生理学。此外，用临床上有效的抗痉挛剂治疗后测量到的一致的抗痉挛效果表明该模型可以有效地用于筛选新的抗痉挛化合物或旨在调节慢性脊柱创伤相关的肌肉痉挛的程序。
The development of spinal hyper-reflexia as part of the spasticity syndrome represents one of the major complications associated with chronic spinal traumatic injury (SCI). The primary mechanism leading to progressive appearance of muscle spasticity is multimodal and may include loss of descending inhibitory tone, alteration of segmental interneuron-mediated inhibition and/or increased reflex activity to sensory input. Here, we characterized a chronic thoracic (Th 9) complete transection model of muscle spasticity in Sprague-Dawley (SD) rats. Isoflurane-anesthetized rats received a Th9 laminectomy and the spinal cord was transected using a scalpel blade. After the transection the presence of muscle spasticity quantified as stretch and cutaneous hyper-reflexia was identified and quantified as time-dependent changes in: i) ankle-rotation-evoked peripheral muscle resistance (PMR) and corresponding electromyography (EMG) activity, ii) Hoffmann reflex, and iii) EMG responses in gastrocnemius muscle after paw tactile stimulation for up to 8 months after injury. To validate the clinical relevance of this model, the treatment potency after systemic treatment with the clinically established anti-spastic agents baclofen (GABAB receptor agonist), tizanidine (α2-adrenergic agonist) and NGX424 (AMPA receptor antagonist) was also tested. During the first 3 months post spinal transection, a progressive increase in ankle rotation-evoked muscle resistance, Hoffmann reflex amplitude and increased EMG responses to peripherally applied tactile stimuli were consistently measured. These changes, indicative of the spasticity syndrome, then remained relatively stable for up to 8 months post injury. Systemic treatment with baclofen, tizanidine and NGX424 led to a significant but transient suppression of spinal hyper-reflexia. These data demonstrate that a chronic Th9 spinal transection model in adult SD rat represents a reliable experimental platform to be used in studying the pathophysiology of chronic spinal injury-induced spasticity. In addition a consistent anti-spastic effect measured after treatment with clinically effective anti-spastic agents indicate that this model can effectively be used in screening new anti-spasticity compounds or procedures aimed at modulating chronic spinal trauma-associated muscle spasticity.