Imaging Cell Based Treatment of Traumatic Brain Injury

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（TBI）后功能恢复的手段;和2）早期（即在损伤后24小时内）用骨髓基质细胞（MSC）治疗TBI，作为神经保护和神经恢复治疗。使用MSC的TBI的神经恢复治疗已经证明在促进神经元重塑和改善功能恢复方面有希望。然而，我们和其他人还没有研究在损伤后24小时内早期用MSC治疗的有益效果。此外，迫切需要无创监测脑重塑和功能恢复，并将这些方法从实验研究转化为临床。我们建议MRI可以灵敏地监测TBI后反映神经功能的脑组织正在进行的结构重塑，因此，MRI可以用于评估恢复并最终应用于TBI患者。在这个提议中，我们将开发和实施MR方法来研究早期和晚期MSC治疗对TBI后MSC迁移和分布以及病变体积的影响（目的1），神经突重组（目的2），以及实验动物脑重塑和功能恢复之间的关系（目的3）。将使用三维激光扫描共聚焦显微镜和免疫组织化学来验证脑重塑的MRI测量。将使用一系列行为测试来评估神经系统结果。有了这些新的方法，我们希望MRI方法测量的分布和浓度的MSC和神经突重组是有效的新工具，用于监测恢复治疗后从TBI的恢复。这些方法应导致治疗方案的优化和改善TBI恢复的管理。 公共卫生相关性：利用脑神经突重组和骨髓基质细胞（MSC）分布的MR测量来预测创伤性脑损伤（TBI）后脑功能恢复的TBI的早期MSC治疗的研究，可以承诺旨在改善TBI恢复的新的患者治疗。这些研究有可能大大提高TBI的神经功能结局，并无创监测相关的神经突起重组，从而恢复功能。

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.