Spreading Depolarizations and Perfusion in Non-traumatic Spinal Cord Injury

脊髓型颈椎病(CSM)是老年人脊髓损伤的最常见原因。它是 以脊髓受到物理压迫为特征，通常在几个月到几年的时间里逐渐进展， 表现为虚弱、麻木和疼痛。因为这是一种不成比例地影响衰老的疾病 人口和导致生活质量下降，它与退伍军人高度相关。许多CSM患者 手术干预后有良好的结果，但有机会通过机械手段改善结果 了解疾病过程和改进的诊断标记物将有助于提高诊断水平 和患者管理，有可能导致治疗方法的改进。这个项目的目的是考察 在临床前动物模型中CSM的扩散性去极化和灌注缺陷的研究。传播 去极化(SD)是一种通过中枢神经系统传播的异常离子波和电波 侮辱后的纸巾。虽然在急性物理创伤后，抑郁症已经得到了很好的确立和特征， 他们还没有被研究过脊髓持续或重复的物理压迫，即 CSM的标志。此外，十二烷基硫酸钠和潜在的血流灌注不足是紧密耦合的。神经元有足够的 氧气和葡萄糖可以从SDS中恢复，但缺乏足够代谢底物的神经元有很高的 受到十二烷基硫酸钠不可挽回的损害的可能性。该项目将使用动物模型和电生理学 在连续或动态物理背景下描述脊髓中SD事件的记录 压缩(目标1)。同时，它将使用mri或椎管内检查脊髓的灌注缺陷。 进行性脊髓脊髓型颈椎病临床相关动物模型中的压力传感器 压缩(目标2)。总之，这些研究将阐明脊髓型颈椎病脊髓损伤的机制。 并可能为诊断标志物提供新的途径。磁共振成像无创性检测异常血流灌注 为后续对CSM患者的临床研究提供了明确的翻译途径。这一项目的调查组 在所有不同的学科领域拥有个人专业知识，并结合多学科方法 这些研究将共同检验一个新的研究领域，具有潜在的高度临床相关性和翻译价值 机遇。

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord damage in older adults. It is characterized by physical compression of the spinal cord and often progresses gradually over months to years, manifesting as weakness, numbness, and pain. Because it is a disease that disproportionately affects an aging population and leads to decreased quality of life, it has a high relevance to Veterans. Many patients with CSM have favorable outcomes after surgical intervention, but opportunities to improve outcomes through mechanistic understanding of the disease process and improved diagnostic markers would be beneficial to improve diagnosis and patient management, potentially leading to improvements in therapies. This project aims to examine the role of spreading depolarization and perfusion deficits in the context of CSM in preclinical animal models. Spreading depolarization (SD) is an abnormal wave of ionic and electrical that propagates through central nervous system tissues after an insult. While SDs have been well-established and characterized after acute physical trauma, they have not been investigated with persistent or repetitive physical compression of the spinal cord that is the hallmark of CSM. Further, SDs and underlying perfusion deficits are tightly coupled. Neurons with sufficient oxygen and glucose can recover from SDs, but neurons that are lack sufficient metabolic substrates have a high likelihood of being irreparably damaged by SDs. This project will use an animal model and electrophysiological recordings to characterize SD events in the spinal cord in the context of continuous or dynamic physical compression (Aim 1). In parallel, it will examine the perfusion deficits in the spinal cord using MRI or intraspinal pressure sensors in the context of a clinically relevant animal model of CSM with progressive spinal cord compression (Aim 2). Collectively, these studies will elucidate the mechanisms of spinal cord damage in CSM and may provide new avenues for diagnostic markers. Detecting abnormal perfusion noninvasively with MRI has a clear translational path for subsequent clinical studies of CSM patients. The team of investigators on this project have individual expertise in all of the different subject areas, and their combined multi-disciplinary approach to these studies will collectively examine a new research area with potential high clinical relevance and translational opportunities.