Detection of Live Fibers in Injured Spinal Cord

检测受损脊髓中的活纤维

• 批准号: 7094705
• 负责人: Mehmet Bilgen
• 金额: $ 19.85万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-20 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094705
• 关键词: injury; manganese; model; role; sectioning; spinal cord; tissues

DESCRIPTION (provided by applicant): Magnetic resonance imaging (MRI) provides in vivo 3D images of rat spinal cord (SC) with exquisite soft tissue contrast, and allows following the same animal longitudinally in experimental spinal cord injury (SCI) studies. Conventional MRIs, however, give limited information and new neuroimaging methods are required for visualizing the neural network of injured SC. Experienced with the use of MR contrast agents in our previous SCI studies, we have investigated manganese-enhanced MRI (MEI) with the potential to produce high-resolution maps of the neural fiber projections in normal and injured cords. Our initial data showed that the contrast agent manganese (Mn) spreads in both rostral and caudal directions in normal cord. In hemisectioned SCs, Mn is transported below the lesion on the contra-lateral, but not ipsilateral, to the cut. This was also confirmed by parallel studies with histological neuronal tracer. In a contusion-type SCI model, Mn labeling was detected within and below the injury, possibly due to the presence of viable tissue therein. In recent experiments, we delivered Mn into the cortex or brainstem of normal and injured rats. With intracortical injection, weak labeling was observed in the descending spinal tracts below the pyramidal decussation. But, injection to brainstem successfully produced sensitive and specific labeling in the targeted fibers. The sections of injured cord below the injury were labeled with Mn, suggesting some fibers were bridging across the injury. From these aspects, MEI offers a new tool for detecting live fibers (spared/restored) in injured SC, and may play a role in validating the accuracy of diffusion tensor imaging (DTI) in sensing these fibers. Based on these results, we hypothesize that DTI corroborated with MEI may provide crucial information on the spatiotemporal dynamics of the changes in the fiber connections during the course of recovery from SCI. To test this hypothesis, we propose to investigate normal and injured SCs using MEI, DTI and high resolution MRI along with neurobehavioral tests and end point histological analysis. These multi-modal studies will establish a new modality to probe the evolution of SCI and map the fiber projections. This should form a basis for future experimental investigations aimed at testing new therapies for promoting fiber connectivity, understanding SC plasticity and improving functional recovery from SCI.

描述（由申请人提供）：磁共振成像（MRI）提供了大鼠脊髓（SC）的体内3D图像，并具有精美的软组织对比度，并允许在实验性脊髓损伤（SCI）研究中纵向遵循相同的动物。但是，传统的MRI提供有限的信息和新的神经影像学方法来可视化受伤的SC的神经网络。在我们以前的SCI研究中使用MR对比剂的经验，我们已经研究了锰增强的MRI（MEI），有可能在正常和受伤的绳索中生成神经纤维投影的高分辨率图。我们的初始数据表明，对比剂锰（MN）在正常绳索中散布在尾部和尾部方向上。在半镜的SC中，MN在相反的外侧（但不是同侧）的病变下方运输到切口。与组织学神经元示踪剂的平行研究也证实了这一点。在挫伤型SCI模型中，在损伤内部和低下发现了MN标记，这可能是由于其中存在可行的组织。在最近的实验中，我们将MN输送到正常和受伤大鼠的皮质或脑干中。使用皮质内注射，在锥体de骨下方的脊柱下降中观察到弱标记。但是，对脑干的注射成功地产生了靶向纤维中的敏感和特定的标记。损伤下方的受伤线的切片用MN标记，表明某些纤维在损伤中桥接。从这些方面，MEI提供了一种新的工具，用于检测受伤的SC中的活纤维（幸免/恢复），并可能在验证传感这些纤维时验证扩散张量成像（DTI）的准确性方面发挥作用。基于这些结果，我们假设用MEI证实的DTI可能会提供有关在SCI恢复过程中光纤连接变化的时空动力学的关键信息。为了检验这一假设，我们建议使用MEI，DTI和高分辨率MRI以及神经行为测试以及终点组织学分析研究正常和受伤的SC。这些多模式研究将建立一种新的模式，以探测SCI的演变并绘制纤维投影。这应该为未来的实验研究构成旨在测试新疗法的实验研究的基础，以促进纤维连通性，了解SC可塑性并改善SCI的功能恢复。