Evaluating Reversible Spinal Fixation in Biped Rats

描述(由申请者提供)：我们建议开发和评估一部小说 可操作脊柱损伤(半脱位)的双足大鼠模型。 设计良好的动物模型是这种脊柱损伤的迫切需要 评估当前理论模型所预测的结果 脊椎手法的机制。我们团队最近设计了一款 收集关于可操作损伤的四足动物模型的数据 提供了非常有趣的信息。尽管四足动物模型已经被 有用的是，从这样一个模型中获得的信息可以应用的程度 对于两足动物人类来说，这是一个仍然没有答案的问题。我们建议合并 双足大鼠脊柱可逆性的独特生物力学特征 在四足大鼠身上发展了固定方法。这一新的组合模式将 让我们对解剖学和生理学有更好的了解 在很大程度上基于两足动物的姿势而产生的差异。这个 结果增加了对脊柱固定对关节的影响的理解 两足动物的脊椎应该会增加我们推断在 从动物研究到临床试验研究和临床实践。因此， 在Proposed研究中，专门设计的脊柱连接装置(SAU)将 手术固定于大鼠L4、L5、L6棘突 它们已经准备好了，并被抬起来用两足动物的姿势行走。之后 术后恢复，SAU外固定8周。这个 LINKS将被用来将椎骨固定在一半的中立位置 被连接的动物的另一半处于弯曲位置。其他动物 将有8周的链接附加，然后删除8周( 模型允许轻松地“分离”脊柱连接单元)。取消链接将 允许我们研究固定后重建运动的效果。 将使用三个年龄匹配的对照组：1)使用SAU的动物，但 没有关联，2)接受假SAU手术的动物，以及3) 根本不做脊椎手术。生物力学测试将评估相对 所有动物的脊柱僵硬：所有动物都将被安乐死， 将对关节突关节进行宏观退变研究。 (骨赘发育、关节表面粗糙、凹坑、隆起和 重塑)。最后，检查脊髓是否有两处改变。 神经肽P物质和降钙素基因相关肽。悬而未决 建议研究的结果，我们会向 脊柱手法治疗节段性颈椎病的疗效评价 脊柱僵硬，关节退变，以及使用 双足脊柱固定模型。这一进步的学习计划将允许 被认为与可操作损伤相关的生物学机制的评估 (半脱位)并脊椎手法与整脊疗法临床 经验。

DESCRIPTION (provided by applicant): We propose to develop and evaluate a novel bipedal rat model of the manipulable spine lesion (the subluxation). Well-designed animal models is of this spine lesion are sorely needed to evaluate outcomes that are predicted by current theoretical models explaining the mechanism of spinal manipulation. Our group has recently designed and collected data on a quadruped rat model of the manipulable lesion that is providing very interesting information. Although the quadruped model has been useful, the degree to which information gained from such a model can be applied to the biped human is a question that remains unanswered. We propose to merge the unique biomechanical features of the bipedal rat with our reversible spinal fixation approach developed in the quadruped rat. This new combined model will allow us to develop a better understanding of anatomic and physiologic differences that occur largely on the basis of the bipedal stance. The resulting increased understanding of the effects of spinal fixation on the bipedal spine should increase our ability to extrapolate information gained in the animal study to clinical trials research and clinical practice. Therefore, in the proposes study, specially designed spinal attachment units (SAUs) will be surgically attached to the L4, L5, and L6 lumbar spinous processes of rats that have been prepared and, raised to walk with a bipedal stance. After post-surgical recovery, the SAUs will be externally linked for 8 weeks. The links will be applied to "fix" the vertebrae in a neutral position in one-half of the linked animals and in a flexed position in the other half. Other animals will have the links attached for 8 weeks and then removed for 8 weeks (the model permit easy "unlinking" of the spinal attachment units). Unlinking will permit us to study the effects of re-establishing motion following fixation. Three age-matched controls will be used: 1) animals with the SAUs applied but not linked, 2) animals that undergo a sham SAU surgery, and 3) animals that have no spinal surgery at all. Biomechanical testing will evaluate relative spine stiffness in all animals: All animals will be euthanized and the zygapophysial joints will be studied macroscopically for degeneration (osteophyte development, articular surface roughing, pitting, elevations, and remodeling). Lastly, the spinal cord will be examined for changes in two neuropeptides substance P and calcitonin gene related peptide. Pending the results of the proposed study, we will submit an R0I grant application to evaluate the effectiveness of spinal manipulation as a treatment for segmental spine stiffness, joint degeneration, and neurophysiologic changes using the bipedal spinal fixation model. This progressive plan of study will permit evaluation of biological mechanisms thought to link the manipulable lesion (subluxation) with spinal manipulation and the chiropractic clinical experience.