Imaging of Brain Remodeling and Functional Recovery

大脑重塑和功能恢复的成像

• 批准号: 7252234
• 负责人: QUAN JIANG
• 金额: $ 46.18万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7252234
• 关键词: Acute; Age; Animals; Anisotropy; Area; Blood Vessels; Blood Volume; Brain imaging; Cerebrovascular Circulation; Cerebrum; Cyclic GMP; Data; Development; Diagnostic; Disease; Elderly; Event; Ferritin; Funding; Glean; Goals; Histocytochemistry; Histology; Human; Image; Immunohistochemistry; Laser Scanning Confocal Microscopy; Lasers; Lead; Magnetic Resonance Imaging; Measurement; Measures; Methods; Monitor; Nervous System Physiology; Neurodegenerative Disorders; Neurons; Outcome; Patients; Predisposition; Rattus; Recovery; Recovery of Function; Research; Scanning; Stroke; Structure; Therapeutic; Thinking; Tissues; Transgenes; Treatment Protocols; Vascular Permeabilities; Vascular remodeling; Weight; aged; angiogenesis; base; behavior test; brain tissue; density; functional outcomes; improved; indexing; inhibitor/antagonist; innovation; nerve injury; neuroblast; neurorestoration; novel; phosphoric diester hydrolase; post stroke; restorative treatment; sildenafil; stroke recovery; tool

The objective of this project is to develop magnetic resonance imaging (MRI) as a tool to non- invasively evaluate and monitor recovery in stroke patients. Our studies during the current funding period indicate that certain agents can enhance functional recovery after stroke in experimental animals based on histological and functional assessments. A prime candidate among restorative agents is sildenafil, a phosphodiesterase type-5 inhibitor, which has been widely used in humans to increase cyclic guanosine monophosphate (cGMP). Our data show that sildenafil significantly improves functional recovery in both young and aged animals after stroke. Hence, we will employ sildenafil in the proposed studies. We have also generated preliminary imaging data, which indicate that certain MRI methods may be sensitive to post-stroke tissue remodeling (vascular and neuronal) events that are thought to influence eventual outcome. The studies proposed in the current application expand on this theme by combining and applying these novel imaging, histological and restorative treatment strategies to assess post-stroke vascular (Aim 1) and neuronal (Aim 2) remodeling in both young and aged animals with and without restorative therapy. MRI will be used to identify, characterize and define tissue-remodeling events that contribute to improvement of late-term functional outcome after stroke. These MRI assessments will be compared and correlated to corresponding measures of tissue remodeling determined from 3D laser scanning confocal microscopy and immunohistochemistry. Finally, Aim 3 will study the relationship between the various MRI and histological indices of neuronal and vascular remodeling and will relate these data to functional outcome as measured by a battery of behavioral tests. The proposed studies are novel and innovative, moving our research away from acute diagnostics and neuroprotective therapeutic approaches for stroke treatment and toward a relatively unexplored area of late-term restorative therapy that promotes brain tissue remodeling events that ultimately improve functional outcome. If successful, these studies are expected to generate ground breaking information about post-stroke brain tissue remodeling that will be useful for monitoring stroke recovery and may lead to optimization of treatment protocols that would benefit all stroke patients.

该项目的目的是开发磁共振成像（MRI）作为非 - 侵入性评估和监测中风患者的恢复。我们在当前资金期间的研究 周期表明某些药物可以在实验中增强中风后的功能恢复 基于组织学和功能评估的动物。恢复中的主要候选人 代理是Sildenafil，一种磷酸二酯酶5型抑制剂，已被广泛用于人类 增加环鸟嘌呤一磷酸（CGMP）。我们的数据表明西地那非显着 中风后改善年轻动物和老年动物的功能恢复。因此，我们将雇用 西地那非在拟议的研究中。我们还生成了初步成像数据， 表明某些MRI方法可能对中风后组织重塑（血管 被认为会影响最终结果的事件。在 当前的应用程序通过组合和应用这些新型成像来扩展此主题 评估冲程后血管的组织学和恢复治疗策略（AIM 1）和 神经元（AIM 2）在有或没有恢复的年轻动物和老年动物中进行重塑 治疗。 MRI将用于识别，表征和定义组织 - 复制事件 有助于改善中风后晚期功能结果。这些MRI评估 将比较并与确定的组织重塑的相应测量 从3D激光扫描共聚焦显微镜和免疫组织化学。最后，AIM 3将学习 神经元和血管的各种MRI和组织学指数之间的关系 重塑，并将这些数据与功能结果相关联 行为测试。拟议的研究是新颖而创新的，使我们的研究远离 急性诊断和中风治疗的神经保护治疗方法 促进脑组织重塑的晚期恢复治疗相对未开发的区域 最终改善功能结果的事件。如果成功的话，这些研究应 生成有关势后脑组织重塑的开创性信息，这将是有用的 用于监测中风的恢复，并可能导致优化治疗方案 使所有中风患者受益。