Bilateral Contusion-Compression Model of Incomplete Traumatic Cervical Spinal Cord Injury
Bilateral Contusion-Compression Model of Incomplete Traumatic Cervical Spinal Cord Injury
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DOI：
10.1089/neu.2014.3388
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发表时间：
2014-11-01
影响因子：
4.2
通讯作者：
Fehlings, Michael G.
中科院分区：
文献类型：
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作者：
Forgione, Nicole;Karadimas, Spyridon K.;Fehlings, Michael G.
尽管颈脊髓损伤（cSCI）的发病率和患病率不断增加，但我们缺乏临床相关的动物模型，可用于研究这种损伤的病理机制和测试新的治疗方法。在这里，我们描述了一个中度颈椎挫伤压缩模型大鼠，类似于不完全创伤性cSCI在人类。我们在8周的恢复期内描述了颈部C6节段18 g夹压损伤的影响。使用Luxol坚牢蓝/苏木精-伊红染色结合定量体视学，我们确定18-g损伤导致灰质（GM）、白色物质（WM）丢失以及空洞形成。磁转移和T2加权磁共振成像被用来分析在体内病变动力学。该分析表明，两种技术都能够区分损伤中心、软膜下边缘和损伤远端的WM。使用Basso、Beattie和Bresnahan（BBB）评分和CatWalk对运动功能进行神经行为评估，发现C6夹压损伤恢复有限。使用握力测试前肢功能显示出显著的前肢功能障碍，与在人类cSCI中观察到的上肢运动功能丧失相似。从前肢记录的感觉诱发电位和从后肢记录的霍夫曼反射证实了我们的神经行为分析中观察到的前肢和后肢缺陷。在这里，我们描述了不完全cSCI的夹压模型，该模型密切模拟了人类的这种情况。这项工作直接解决了目前缺乏临床相关模型的cSCI，因此将有助于提高成功的翻译推定的治疗到临床。
Despite the increasing incidence and prevalence of cervical spinal cord injury (cSCI), we lack clinically relevant animal models that can be used to study the pathomechanisms of this injury and test new therapies. Here, we characterize a moderate cervical contusion-compression model in rats that is similar to incomplete traumatic cSCI in humans. We characterized the effects of 18-g clip-compression injury at cervical level C6 over an 8-week recovery period. Using Luxol fast blue/hematoxylin-eosin staining in combination with quantitative stereology, we determined that 18-g injury results in loss of gray matter (GM), white matter (WM), as well as in cavity formation. Magnetization transfer and T2-weighted magnetic resonance imaging were used to analyze lesion dynamics in vivo. This analysis demonstrated that both techniques are able to differentiate between the injury epicenter, subpial rim, and WM distal to the injury. Neurobehavioral assessment of locomotor function using Basso, Beattie, and Bresnahan (BBB) scoring and CatWalk revealed limited recovery from clip-compression injury at C6. Testing of forelimb function using grip strength demonstrated significant forelimb dysfunction, similar to the loss of upper-limb motor function observed in human cSCI. Sensory-evoked potentials recorded from the forelimb and Hoffman reflex recorded from the hindlimb confirmed the fore- and hindlimb deficits observed in our neurobehavioral analysis. Here, we have characterized a clip-compression model of incomplete cSCI that closely models this condition in humans. This work directly addresses the current lack of clinically relevant models of cSCI and will thus contribute to improved success in the translation of putative therapies into the clinic.