Center for Stroke Research

中风研究中心

• 批准号: 7418306
• 负责人: MICHAEL CHOPP
• 金额: $ 90.86万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418306
• 关键词: Center; Stroke; Research

DESCRIPTION (provided by applicant): This competing renewal (year 20) Program Project application pioneers the development of neurorestorative treatment of stroke and the application of magnetic resonance imaging (MRI) as a means to monitor neuronal and vascular structural changes in brain as they relate to functional improvement. Our preclinical data demonstrate significant improvement in neurological function after treatment of stroke in both young and old animals with sildenafil, a phosphodiesterase type 5 inhibitor which increases cyclic guanosine monophosphate (cGMP) in brain. To bring neurorestorative therapy to clinical fruition, we propose three highly integrated and longitudinally designed projects. Project 1 investigates with and without sildenafil treatment, the cellular and molecular mechanisms responsible for neuroblast proliferation in the subventricular zone of brain and their migration to the site of ischemia, the interaction of the microvasculature in the ischemic brain with these migrating neuroblasts, and the signal transduction pathways which mediate neurogenesis and angiogenesis. In Project 2, we translate the basic science in Project 1 into a preclinical study of restorative neurogenesis and angiogenesis in rodents subjected to embolic stroke and treated with sildenafil. In this project, we emphasize imaging of the neuronal and vascular remodeling processes in brain. We employ MRI, specifically, fractional anisotropy to image neuronal changes, and a cluster of MR methods to identify vascular remodeling in the ischemic brain. MRI indices of neuronal and vascular remodeling are thus related to functional and behavioral outcome, with the goal of developing MRI as a marker of recovery after stroke. We also develop novel approaches to measure neuroblast migration, and we employ two-photon laser scanning confocal microscopy to visualize in real-time vascular and neurite structure with the goals of developing neurorestorative treatment of stroke and obtaining fundamental and new information on the dynamic processes of brain remodeling post stroke. Project 3 is a Phase I safety clinical trial using sildenafil as a neurorestorative treatment of stroke patients with treatment administered within 7 days of stroke onset. As in Project 2, MRI will be employed to identify neuronal and vascular changes in the human brain and to relate these changes to functional recovery. The three projects are supported by three cores. Core A is the Administrative Core, Core B is the Statistical and Data Management Core and Core C is an Imaging Core. The long-term objectives of this Program Project are to develop neurorestorative therapy for stroke and MRI methods to noninvasively monitor neuronal and vascular changes reflecting recovery from stroke. Our studies are designed to improve neurological function and the management of the stroke patient.

描述（由申请人提供）： 这项竞争更新（第 20 年）计划项目申请开创了中风神经恢复治疗的发展，以及磁共振成像 (MRI) 作为监测大脑神经元和血管结构变化的手段的应用，因为它们与功能改善有关。我们的临床前数据表明，用西地那非（一种 5 型磷酸二酯酶抑制剂，可增加大脑中的环鸟苷酸 (cGMP)）治疗中风后，年轻和年老动物的神经功能均得到显着改善。为了将神经修复疗法推向临床，我们提出了三个高度整合和纵向设计的项目。项目 1 研究有和没有西地那非治疗、脑室下区神经母细胞增殖及其迁移到缺血部位的细胞和分子机制、缺血脑中微脉管系统与这些迁移神经母细胞的相互作用以及信号介导神经发生和血管发生的转导途径。在项目 2 中，我们将项目 1 中的基础科学转化为对患有栓塞性中风并接受西地那非治疗的啮齿动物的恢复性神经发生和血管生成的临床前研究。在这个项目中，我们强调大脑神经元和血管重塑过程的成像。我们采用 MRI，特别是分数各向异性来对神经元变化进行成像，并使用一系列 MR 方法来识别缺血性大脑中的血管重塑。因此，神经元和血管重塑的 MRI 指数与功能和行为结果相关，目标是将 MRI 开发为中风后恢复的标志。我们还开发了测量神经母细胞迁移的新方法，并采用双光子激光扫描共聚焦显微镜来实时可视化血管和神经突结构，目的是开发中风的神经恢复治疗方法并获得有关神经母细胞动态过程的基本和新信息。中风后的大脑重塑。项目 3 是一项 I 期安全临床试验，使用西地那非作为中风患者的神经恢复治疗，并在中风发作 7 天内进行治疗。与项目 2 一样，MRI 将用于识别人脑中的神经元和血管变化，并将这些变化与功能恢复联系起来。这三个项目由三个核心支撑。核心 A 是管理核心，核心 B 是统计和数据管理核心，核心 C 是成像核心。该计划项目的长期目标是开发中风神经恢复疗法和 MRI 方法，以无创监测反映中风恢复情况的神经元和血管变化。我们的研究旨在改善神经功能和中风患者的治疗。

项目成果

Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic.

• DOI: 10.1016/s1474-4422(09)70061-4
• 发表时间: 2009-05
• 期刊: LANCET NEUROLOGY
• 影响因子: 48
• 作者: Zhang, Zheng Gang;Chopp, Michael
• 通讯作者: Chopp, Michael

Synergistic effect of an endothelin type A receptor antagonist, S-0139, with rtPA on the neuroprotection after embolic stroke.

• DOI: 10.1161/strokeaha.108.515684
• 发表时间: 2008-10
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Zhang RL;Zhang C;Zhang L;Roberts C;Lu M;Kapke A;Cui Y;Ninomiya M;Nagafuji T;Albala B;Zhang ZG;Chopp M
• 通讯作者: Chopp M

Clustering method for estimating principal diffusion directions.

• DOI: 10.1016/j.neuroimage.2011.05.056
• 发表时间: 2011-08-01
• 期刊: NEUROIMAGE
• 影响因子: 5.7
• 作者: Nazem-Zadeh, Mohammad-Reza;Jafari-Khouzani, Kourosh;Davoodi-Bojd, Esmaeil;Jiang, Quan;Soltanian-Zadeh, Hamid
• 通讯作者: Soltanian-Zadeh, Hamid

Increasing Ang1/Tie2 expression by simvastatin treatment induces vascular stabilization and neuroblast migration after stroke.

• DOI: 10.1111/j.1582-4934.2008.00380.x
• 发表时间: 2009-07
• 期刊: Journal of cellular and molecular medicine
• 影响因子: 5.3
• 作者: Chen J;Cui X;Zacharek A;Chopp M
• 通讯作者: Chopp M

MRI detects brain reorganization after human umbilical tissue-derived cells (hUTC) treatment of stroke in rat.

• DOI: 10.1371/journal.pone.0042845
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Jiang Q;Thiffault C;Kramer BC;Ding GL;Zhang L;Nejad-Davarani SP;Li L;Arbab AS;Lu M;Navia B;Victor SJ;Hong K;Li QJ;Wang SY;Li Y;Chopp M
• 通讯作者: Chopp M