Imaging Cell Based Treatment of Traumatic Brain Injury

描述（由申请人提供）：我们的提案有两个主要的创新方面：1)发展磁共振成像（MRI）作为一种监测和预测创伤性脑损伤（TBI）后功能恢复的手段；2)早期（即损伤后24小时内）应用骨髓基质细胞（MSCs）治疗TBI，作为神经保护和神经修复疗法。利用间充质干细胞进行脑损伤的神经修复治疗，在促进神经元重塑和改善功能恢复方面具有良好的前景。然而，我们和其他人尚未研究损伤后24小时内早期使用间充质干细胞治疗的有益效果。此外，迫切需要无创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研究。我们认为MRI可以灵敏地监测脑外伤后脑组织的结构重塑，反映神经功能，因此MRI可以用来评估恢复情况，并最终应用于脑外伤患者。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MSCs迁移和分布以及病变体积（Aim 1），神经突重组（Aim 2）以及脑重塑与功能恢复（Aim 3）之间的关系的影响。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。神经系统的结果将通过一系列行为测试来评估。有了这些新方法，我们期望MRI方法测量间充质干细胞的分布和浓度以及神经突重组是监测恢复性治疗后TBI恢复的有效新工具。这些方法将导致治疗方案的优化和TBI恢复管理的改进。

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.