Modeling spinal cord contusion, dislocation, and distraction: Characterization of vertebral clamps, injury severities, and node of Ranvier deformations

Modeling spinal cord contusion, dislocation, and distraction: Characterization of vertebral clamps, injury severities, and node of Ranvier deformations
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DOI:
10.1016/j.jneumeth.2009.04.007
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发表时间:
2009-06-30
影响因子:
3
通讯作者:
Oxland, Thomas R.
Oxland, Thomas R.
中科院分区:
医学4区
文献类型:
--
作者:
Choo, Anthony Min-Te;Liu, Jie;Oxland, Thomas R.

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脊髓挫伤和横断模型是研究脊髓损伤的常用模型。然而,在临床上,其他生物力学损伤机制,如椎体脱位和牵引经常发生,但这些损伤是很难在动物中产生。我们机械特性的椎骨夹紧策略,使建模的椎骨脱位和牵引损伤,除了标准的挫伤范例-在大鼠颈椎。这些椎骨夹的刚度为83.6 +/- 18.9 N/mm,夹持强度为64.7 +/- 10.2 N,允许在高速(类似于100 cm/s)下对损伤进行建模。Logistic回归分析表明,中度至重度损伤,急性死亡率为10%,发生在C4/5背腹脱位2.6 mm和C4和C5之间的喙尾牵引4.1 mm处。脱位和牵张造成的损伤表现出在挫伤中不存在的轴突损伤的特征。我们进行了形态计量学分析,在节点的Ranvier使用免疫组化钾通道(Kv1.2)在arctaparanodal区域。牵张损伤后,观察到朗维尔淋巴结延长至病变头侧4 mm。与此相反,挫伤产生的扭曲,在结节的几何形状,仅限于附近的病变。在位错的震中处,郎维几何学的节点变形最大。鉴于白色损伤在SCI病理学中的重要性,这些损伤模式的独特性表明脱位和牵张损伤模型补充了现有的挫伤模型。总之,这三种动物模型跨越了更广泛的临床范围,可以更可靠地衡量治疗策略的潜在人类疗效。(C)2009爱思唯尔有限公司版权所有。
Spinal cord contusion and transection models are widely used for studying spinal cord injury (SCI). Clinically, however, other biomechanical injury mechanisms such as vertebral dislocation and distraction frequently occur, but these injuries are difficult to produce in animals. We mechanically characterize a vertebral clamping strategy that enables the modeling of vertebral dislocation and distraction injuries in addition to the standard contusion paradigm - in the rat cervical spine. These vertebral clamps have a stiffness of 83.6 +/- 18.9 N/mm and clamping strength 64.7 +/- 10.2 N which allows injuries to be modeled at high-speed (similar to 100 cm/s). Logistic regression indicated that a moderate-to-severe injury, with an acute mortality rate of 10%, occurs at 2.6 mm of C4/5 dorso-ventral dislocation and 4.1 mm of rostro-caudal distraction between C4 and C5. Injuries produced by dislocation and distraction exhibited features of axonal damage that were absent in contusion injuries. We conducted morphometric analysis at the nodes of Ranvier using immunohistochemistry for potassium channels (Kv1.2) in the juxtaparanodal region. Following distraction injuries, elongated nodes of Ranvier were observed up to 4 mm rostral to the lesion. In contrast, contusion injuries produced distortions in nodal geometry which were restricted to the vicinity of the lesion. The greatest deformations in node of Ranvier geometry occurred at the dislocation epicenter. Given the importance of white matter damage in SCI pathology, the distinctiveness of these injury patterns demonstrate that the dislocation and distraction injury models complement existing contusion models. Together, these three animal models span a broader clinical spectrum for more reliably gauging the potential human efficacy of therapeutic strategies. (C) 2009 Elsevier B.V. All rights reserved.