Imaging Cell Based Treatment of Traumatic Brain Injury

基于细胞成像的脑外伤治疗

• 批准号: 8272524
• 负责人: QUAN JIANG
• 金额: $ 32.04万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8272524
• 关键词: Acute; Animals; Anisotropy; Bone Marrow; Bone Marrow Transplantation; Brain; Cell Therapy; Cell Transplantation; Cells; Cerebrum; Clinic; Data; Development; Exhibits; Goals; Histocytochemistry; Hour; Image; Injury; Investigation; Knowledge; Label; Laser Scanning Confocal Microscopy; Lead; Lesion; Magnetic Resonance Imaging; Marrow; Measurement; Measures; Methodology; Methods; Monitor; Nature; Nervous System Physiology; Neurites; Neurological outcome; Neurons; Patients; Protocols documentation; Radial; Rattus; Recovery; Recovery of Function; Stromal Cells; Structure; Synapses; Time; Tissues; Translating; Traumatic Brain Injury; Treatment Protocols; base; behavior test; brain remodeling; brain tissue; cell motility; cellular imaging; clinical practice; functional outcomes; improved; indexing; injured; innovation; migration; myelination; neurological recovery; neurorestoration; novel strategies; preclinical study; research study; therapy development; tool

DESCRIPTION (provided by applicant): There are two major innovative aspects to our proposal: 1) To develop magnetic resonance imaging (MRI) as a means to monitor and predict functional recovery after traumatic brain injury (TBI); and 2) To treat TBI with bone marrow stromal cells (MSCs) early, i.e. within 24 hours of injury, as a neuroprotective and neurorestorative therapy. Neurorestorative treatment of TBI using MSCs has demonstrated promise in promoting neuronal remodeling, and improvement of functional recovery. However, we and others have not studied the beneficial effects of early, within 24 hours of injury, treatment with MSCs. Also, there is a compelling need to noninvasively monitor brain remodeling and functional recovery and to translate these methodologies from experimental studies to the clinic. We propose that MRI can sensitively monitor ongoing structural remodeling of brain tissue after TBI that reflects neurological function, and therefore, MRI can be employed to assess recovery and ultimately be applied to the TBI patient. In this proposal, we will develop and implement MR methodologies to investigate the effects of early and late MSC treatment on the migration and distribution of MSCs and lesion volume after TBI (Aim 1), neurite reorganization (Aim 2), and the relationship between brain remodeling and functional recovery (Aim 3) in the experimental animal subjected to TBI. MRI measurements of brain remodeling will be verified using three dimensional laser scanning confocal microscopy and immuno-histochemistry. Neurological outcome will be assessed using a battery of behavioral tests. With these novel approaches, we expect that MRI methodologies for measurement of distribution and concentration of MSCs and neurite reorganization are valid new tools for monitoring the recovery from TBI after restorative therapy. These methods should lead to optimization of treatment protocols and improved management of recovery from TBI.

描述（由申请人提供）：我们的提案有两个主要创新点：1）开发磁共振成像（MRI）作为监测和预测创伤性脑损伤（TBI）后功能恢复的手段； 2) 尽早使用骨髓基质细胞 (MSC) 治疗 TBI，即损伤后 24 小时内，作为神经保护和神经恢复疗法。使用 MSC 进行 TBI 神经修复治疗已证明在促进神经元重塑和改善功能恢复方面具有前景。然而，我们和其他人尚未研究损伤后 24 小时内早期使用 MSC 治疗的有益效果。此外，迫切需要无创地监测大脑重塑和功能恢复，并将这些方法从实验研究转化为临床。我们认为MRI可以灵敏地监测TBI后脑组织正在进行的结构重塑，从而反映神经功能，因此MRI可以用于评估恢复情况并最终应用于TBI患者。在本提案中，我们将开发和实施 MR 方法，以研究早期和晚期 MSC 治疗对 TBI 后 MSC 的迁移和分布以及病灶体积（目标 1）、神经突重组（目标 2）以及大脑之间的关系的影响。遭受 TBI 的实验动物的重塑和功能恢复（目标 3）。大脑重塑的 MRI 测量将使用三维激光扫描共聚焦显微镜和免疫组织化学进行验证。将使用一系列行为测试来评估神经学结果。通过这些新方法，我们期望用于测量 MSC 分布和浓度以及神经突重组的 MRI 方法成为监测恢复性治疗后 TBI 恢复情况的有效新工具。这些方法应该可以优化治疗方案并改善 TBI 恢复的管理。