Evaluating Reversible Spinal Fixation in Biped Rats

评估双足大鼠的可逆脊柱固定

• 批准号: 6534564
• 负责人: Charles N.R. Henderson
• 金额: $ 15.69万
• 依托单位: PALMER COLLEGE OF CHIROPRACTIC
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-10 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534564
• 关键词: biological models; biomechanics; calcitonin gene related peptide; chiropractic; disease /disorder model; implant; joint stiffness; laboratory rat; model design /development; neurophysiology; nonhuman therapy evaluation; orthopedics; spine disorder; substance P; vertebrae

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.

描述（由申请人提供）：我们建议开发和评估一种新的 可操作脊柱损伤（半脱位）的双足大鼠模型。 设计良好的脊柱病变动物模型是迫切需要的， 评估当前理论模型预测的结果， 脊柱推拿的原理我们小组最近设计并 收集了可操作病变的四足大鼠模型的数据，即 提供了非常有趣的信息。尽管四足动物模型已经被 有用，从这种模型中获得的信息可以应用的程度 是一个尚未解决的问题我们提议合并 双足大鼠的独特生物力学特征，我们的可逆脊柱 四足鼠的固定方法。这一新的组合模式将 使我们能够更好地了解解剖和生理 这些差异主要是基于两足站立的基础上发生的。的 从而增加了对脊柱固定对 双足脊椎应该可以增加我们推断信息的能力， 从动物实验到临床试验研究和临床实践。因此，我们认为， 在建议的研究中，专门设计的脊柱附着单元（SAU）将 通过手术连接到大鼠的L4、L5和L6腰椎棘突 它们已经准备好了，并被抬起以两足站立行走。后 手术后恢复，SAU将外部连接8周。的 连接将被用于将椎骨“固定”在一半的中立位置， 而另一半则处于弯曲的位置。其他动物 将有连接8周，然后删除8周（ 模型允许脊柱连接单元容易地“解开”）。解除链接将 允许我们研究固定后重建运动的效果。 将使用三种年龄匹配的对照：1）施用SAU但 不相关，2）接受假SAU手术的动物，和3） 没有做过脊椎手术生物力学测试将评价相对 所有动物的脊柱僵硬：所有动物将被安乐死， 将肉眼观察关节突关节的退化情况 （骨赘发育、关节面粗糙、凹陷、隆起和 重塑）。最后，将检查脊髓的变化， 神经肽P物质和降钙素基因相关肽。等待 建议的研究结果，我们将提交R0I补助金申请， 评价脊柱推拿作为节段性脊柱畸形治疗的有效性 脊柱僵硬、关节退行性变和神经生理学变化， 双足脊柱固定模型。这个渐进的学习计划将允许 评价被认为与可操作病变相关的生物学机制 （半脱位）与脊柱操作和脊椎按摩临床 体验.