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）： 这种竞争性更新（第20年）计划项目的应用先驱，使中风的神经疏松治疗以及磁共振成像（MRI）的应用作为监测与功能改进相关的大脑神经元和血管结构变化的一种手段。我们的临床前数据表明，用西地那非的年轻动物和老年动物（一种磷酸二酯酶5型抑制剂）在治疗中风后的神经功能显着改善，可增加大脑中环状鸟苷单磷酸（CGMP）。为了将神经训练疗法带入临床成果，我们提出了三个高度综合且纵向设计的项目。项目1通过或不进行西地那非治疗，研究了脑部脑静脉内的神经细胞增殖的细胞和分子机制，以及它们转移到缺血部位的迁移，缺血性脑中微胚胎与这些神经细胞迁移的迁移诱导诱导途径的相互作用，以及介导毒素的迁移，并介导了Angiate neurogence and Angiatient neurogeneens，并介导了Angiatient angiatiate angiatiate angientiate angiogen和Angiatiate angiogen ogengen and Angiatient ang angiogen and Angiatient and angiogen and ang viogenegenge。在项目2中，我们将项目1中的基础科学转化为一项临床前研究，该研究对经过栓塞式中风并用西地那非治疗的啮齿动物中的恢复性神经发生和血管生成。在这个项目中，我们强调大脑中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的变化进行图像，以及一组MR方法来鉴定缺血性脑中的血管重塑。因此，神经元和血管重塑的MRI指标与功能和行为结果有关，目的是将MRI作为中风后恢复的标志。我们还开发了测量神经细胞迁移的新方法，并采用两光子激光扫描共聚焦显微镜在实时血管和神经突结构中可视化，目的是开发中风的神经训练治疗，并获得有关脑重新脑化后脑脑重建后的基本信息和新的信息。项目3是一项I期安全临床试验，使用西地那非作为中风发作后7天内治疗的中风患者的神经4t术治疗。与项目2一样，将使用MRI来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。这三个项目得到了三个核心的支持。核心A是管理核心，核心B是统计，数据管理核心和核心C是成像核心。该计划项目的长期目标是开发中风和MRI方法的神经训练疗法，以无创监测反映中风恢复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管理。

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

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

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

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