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.

该项目的目标是开发磁共振成像（MRI）作为一种工具来非 有创评估和监测中风患者的康复情况。我们在当前资助期间的研究 实验表明，某些药物可以增强中风后的功能恢复 基于组织学和功能评估的动物。恢复性的主要候选人 西地那非是一种5型磷酸二酯酶抑制剂，已广泛应用于人类 增加环磷酸鸟苷 (cGMP)。我们的数据显示西地那非显着 改善中风后年轻和老年动物的功能恢复。因此，我们将雇用 拟议研究中的西地那非。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 和神经元）被认为影响最终结果的事件。中提出的研究 当前的应用通过结合和应用这些新颖的成像来扩展这个主题， 评估中风后血管的组织学和恢复性治疗策略（目标 1）和 在有或没有恢复的情况下，年轻和年老动物的神经元（目标 2）重塑 治疗。 MRI 将用于识别、表征和定义组织重塑事件 有助于改善中风后的远期功能结果。这些 MRI 评估 将与确定的组织重塑的相应测量值进行比较和关联 来自 3D 激光扫描共焦显微镜和免疫组织化学。最后，目标3将学习 神经元和血管的各种MRI与组织学指标之间的关系 重塑并将这些数据与通过一组测量的功能结果相关联 行为测试。拟议的研究新颖且具有创新性，使我们的研究远离 中风治疗的急性诊断和神经保护治疗方法 促进脑组织重塑的后期恢复治疗相对尚未探索的领域 最终改善功能结果的事件。如果成功的话，这些研究预计将 生成有关中风后脑组织重塑的突破性信息，这将是有用的 用于监测中风恢复并可能导致治疗方案的优化 造福所有中风患者。