Evaluating Reversible Spinal Fixation in Biped Rats

评估双足大鼠的可逆脊柱固定

• 批准号: 6364230
• 负责人: Charles N.R. Henderson
• 金额: $ 14.71万
• 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 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6364230
• 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部小说 可操作脊柱损伤（半脱位）的双足大鼠模型。 迫切需要精心设计的这种脊柱病变的动物模型 评估当前理论模型预测的结果解释 脊柱操纵机制。我们小组最近设计并 收集了四足大鼠模型的可操作损伤的数据 提供非常有趣的信息。虽然四足动物模型已经 有用，从这种模型获得的信息可以应用的程度 对于两足动物来说，这是一个尚未得到解答的问题。我们建议合并 具有可逆脊柱的双足大鼠独特的生物力学特征 在四足大鼠中开发的固定方法。这种新的组合模型将 使我们能够更好地了解解剖学和生理学 差异主要是基于双足姿势而发生的。这 从而加深了对脊柱固定对脊柱影响的了解 双足脊柱应该提高我们推断所获得信息的能力 从动物研究到临床试验研究和临床实践。所以， 在拟议的研究中，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 已准备好并抬起以双足姿势行走。后 术后恢复后，SAU 将在外部连接 8 周。这 将应用链接将椎骨“固定”在二分之一的中立位置 相连的动物的一部分，另一半处于弯曲的位置。其他动物 将附加链接 8 周，然后删除 8 周（ 模型允许轻松“断开”脊柱附着单元）。取消链接将 允许我们研究固定后重新建立运动的效果。 将使用三个年龄匹配的对照：1）应用了 SAU 的动物，但 不相关，2）接受假 SAU 手术的动物，以及 3） 根本没有做过脊柱手术。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， 将从宏观角度研究关节突关节的退化情况 （骨赘发育、关节表面粗糙、点蚀、隆起和 改造）。最后，将检查脊髓是否有以下两个方面的变化： 神经肽P物质和降钙素基因相关肽。待定 根据拟议研究的结果，我们将向 评估脊柱手法治疗节段性脊柱炎的有效性 脊柱僵硬、关节退化和神经生理学变化 双足脊柱固定模型。这个渐进的学习计划将允许 评估被认为与可操作病变相关的生物学机制 （半脱位）脊柱手法和脊椎按摩临床 经验。