Imaging Cell Based Treatment of Traumatic Brain Injury

基于细胞成像的脑外伤治疗

• 批准号: 8184116
• 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/8184116
• 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. PUBLIC HEALTH RELEVANCE: The investigation of early MSC therapy of TBI utilizing MR-measures of brain neurite reorganization and bone marrow stromal cell (MSC) distribution for predicting brain functional recovery after traumatic brain injury (TBI) and could promise new patient therapies aimed at improving TBI recovery. These studies have the potential to greatly enhance neurological outcomes from TBI and to noninvasively monitor the associated neurite reorganization leading to the recovery of functions.

描述（由申请人提供）：我们的建议有两个主要的创新方面：1）开发磁共振成像（MRI），作为监测和预测创伤性脑损伤后功能恢复的手段（TBI）； 2）早日用骨髓基质细胞（MSC）治疗TBI，即受伤后的24小时内作为神经保护和神经训练疗法。使用MSCS对TBI进行神经训练治疗已表现出在促进神经元重塑和功能恢复改善方面的希望。但是，我们和其他人尚未在受伤后的24小时内研究早期的有益作用。同样，迫切需要非侵入性地监测大脑的重塑和功能恢复，并将这些方法从实验研究转化为诊所。我们建议MRI可以在TBI之后敏感地监测脑组织正在进行的结构重塑，以反映神经功能，因此，可以使用MRI评估恢复并最终应用于TBI患者。在这项提案中，我们将开发和实施MR方法，以研究MSC治疗早期和晚期治疗对TBI后MSC和病变量的迁移和分布的影响（AIM 1），神经突重组（AIM 2）（AIM 2）以及受到TBI的实验动物的脑重塑与功能恢复之间的关系（AIM 3）。将使用三维激光扫描共聚焦显微镜和免疫 - 归化学验证大脑重塑的MRI测量。神经系统结果将使用一系列行为测试评估。通过这些新颖的方法，我们期望MRI方法学用于测量分布和MSC和神经突重组的浓度是监测恢复治疗后从TBI中恢复的有效新工具。这些方法应导致优化治疗方案并改善从TBI恢复的管理。 公共卫生相关性：对早期MSC治疗TBI的研究，利用脑神经神经突重组和骨髓基质细胞（MSC）分布的MR测量，以预测创伤性脑损伤后脑功能恢复（TBI），并可以保证新的患者疗法旨在改善TBI恢复。这些研究有可能大大增强TBI的神经系统结局，并无创地监测相关的神经突重组，从而导致功能的恢复。