Detection of Live Fibers in Injured Spinal Cord

检测受损脊髓中的活纤维

• 批准号: 7500469
• 负责人: Mehmet Bilgen
• 金额: $ 9.09万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 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 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7500469
• 关键词: Affect; Animal Model; Animals; Architecture; Area; Beds; Biological Neural Networks; Brain Stem; Chest; Chronic Phase; Condition; Contrast Media; Contusions; Corticospinal Tracts; Data; Descending Spinal Cord Tract; Detection; Development; Diffusion Magnetic Resonance Imaging; Dorsal; Edema; End Point; Event; Evolution; Fiber; Forelimb; Future; Hemorrhage; Hindlimb; Histology; Image; Immunohistochemistry; Injection of therapeutic agent; Injury; Intervention; Invasive; Investigation; Ipsilateral; Knowledge; Label; Lateral; Lead; Lesion; Life; Location; Longitudinal Studies; Lumbar Regions; Magnetic Resonance Imaging; Manganese; Maps; Measurement; Mediating; Methodology; Methods; Modality; Modeling; Motor; Motor Cortex; Motor Skills; Natural regeneration; Necrosis; Nerve Fibers; Neurologic Deficit; Neurons; Outcome; Play; Process; Prohibit; Pyramidal Tracts; Rattus; Recovery; Recovery of Function; Reporting; Research Personnel; Residual state; Resolution; Role; Score; Side; Signal Transduction; Site; Spinal Cord; Spinal Cord Plasticity; Spinal cord injury; Structure of pyramidal decussation; Structure of rubrospinal tract; Techniques; Testing; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissues; Tracer; base; experience; functional restoration; gray matter; improved; in vivo; injured; insight; neural circuit; neurobehavioral test; neuroimaging; neuronal survival; novel; programs; relating to nervous system; research study; soft tissue; spatiotemporal; time interval; tissue processing; tool; white matter

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.

磁共振成像（MRI）为大鼠脊髓（SC）的体内3D图像提供精美的软 组织对比，并允许在实验性脊髓损伤（SCI）中纵向遵循相同的动物 研究。但是，常规MRI需要提供有限的信息和新的神经影像学方法 用于可视化受伤的SC的神经网络。在我们的使用MR对比代理中经验丰富 先前的SCI研究，我们已经研究了锰增强的MRI（MEI），有可能生产 正常和受伤的绳索中神经纤维投影的高分辨率图。我们的最初数据表明 对比剂锰（MN）在正常绳索中散布在尾部和尾部方向上。在 MN的半镜SCS在相反的外侧（但不是同侧）下在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， 在损伤内部和低于损伤内检测到MN标记，这可能是由于其中存在生存的组织。 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。和 在金字塔以下的降脊柱中观察到皮质内注射，弱标记 十二杆。但是，对脑干的注射成功产生了靶向的敏感和特定标记 纤维。受伤下方的受伤线的部分用MN标记，表明某些纤维是 在伤害上桥接。从这些方面，MEI提供了一种用于检测活纤维的新工具 （幸免/恢复）在受伤的SC中，并且可能在验证扩散张量成像的准确性方面发挥作用 （DTI）在感知这些纤维时。基于这些结果，我们假设DTI用MEI证实了 提供有关纤维连接变化的时空动力学的关键信息 从SCI恢复的过程。为了检验这一假设，我们建议研究正常和受伤的SCS 使用MEI，DTI和高分辨率MRI以及神经行为测试和终点组织学分析。 这些多模式研究将建立一种新的方式来探测SCI的演变并绘制光纤 预测。这应该构成旨在测试新疗法的未来实验研究的基础 为了促进纤维连通性，了解SC可塑性并改善SCI的功能恢复。