Effects of global brain health on sensorimotor recovery after stroke

全球大脑健康对中风后感觉运动恢复的影响

• 批准号: 10376049
• 负责人: Sook-Lei Liew
• 金额: $ 61.15万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10376049
• 关键词: Accounting; Acute; Affect; Age; Alzheimer' s Disease; American; Atrophic; Automobile Driving; Behavioral; Blood Vessels; Brain; Brain Injuries; Brain Mapping; Brain imaging; Corticospinal Tracts; Cross-Sectional Studies; Data; Data Collection; Data Set; Databases; Deterioration; Diffusion Magnetic Resonance Imaging; Distant; Factor Analysis; Focal Brain Injuries; Geography; Global Change; Health Care Costs; Image; Individual; Infarction; Injury; Knowledge; Lesion; Link; Longitudinal Studies; Measures; Mission; Modeling; Motor; Motor Evoked Potentials; Neurobiology; Neuronal Plasticity; Outcome; Persons; Population; Process; Public Health; Recovery; Research; Resources; Risk; Role; Sensory; Severities; Site; Spatial Distribution; Stroke; Structure; System; Techniques; Testing; Transcranial magnetic stimulation; Traumatic Brain Injury; United States National Institutes of Health; White Matter Hyperintensity; Work; acute stroke; base; brain health; brain repair; chronic stroke; diffusion anisotropy; effective therapy; experience; improved; indexing; innovation; mortality; neural repair; neuroimaging; new therapeutic target; novel; outcome prediction; post stroke; prospective; research and development; secondary analysis; stroke outcome; stroke patient; stroke recovery; therapeutic development; therapeutic target; working group

PROJECT SUMMARY The neurobiology of post-stroke sensorimotor recovery is not fully understood. Current research on stroke recovery focuses on two spatial levels of brain injury: the focal level (i.e., the lesion and brain structures directly affected by the stroke, such as the corticospinal tract) and the network level (i.e., brain structures distant from the lesion but affected via diaschisis). This proposal argues that a third level should be considered: global brain health (GBH), which is defined as the cellular, structural, and vascular integrity of the whole brain. Although GBH has recently been recognized as a crucial predictor of outcomes in conditions such as Alzheimer’s disease and traumatic brain injury, its role in stroke recovery is not well understood. Similarly, although focal and network effects of stroke injury have been well-studied, little is known about how stroke exerts global influences across the whole brain. The key scientific premise of this research is that (a) GBH modulates the overall neuroplastic resources that promote stroke recovery and (b) acute stroke injury causes global changes in brain health. The central hypothesis is that poor GBH is related to poor stroke outcomes, and conversely, that severe acute stroke injury is related to worsening of GBH. The rationale underlying the proposed research is that establishing GBH as a meaningful contributor to stroke recovery may stimulate new avenues of research and novel targets for therapeutic development. GBH will be estimated as indexed by four brain imaging measures linked to brain health (predicted brain age reflecting structural atrophy, severity of deep white matter hyperintensities, periventricular hyperintensities, and perivascular spaces). Aim 1 will utilize a large, retrospective stroke neuroimaging and behavioral database from the ENIGMA Stroke Recovery working group (N=627) to characterize the relationship between GBH and stroke outcomes in a cross-sectional chronic stroke population. Aim 2 will use a prospective, multi-site, longitudinal data collection (N=144) in individuals within three weeks and at three months after stroke to study how initial GBH relates to post-stroke brain repair and sensorimotor recovery. Aim 3 will use the same prospective dataset (N=144) to examine how the severity of acute stroke relates to longitudinal changes in GBH between 3 weeks and 3 months. With respect to key findings, we expect to show that GBH is related to sensorimotor outcomes and predicts the extent of early stroke recovery, and that GBH evolves in this context. The proposed work is innovative because it opens an entirely new framework in which to consider sensorimotor recovery after stroke. The results are expected to have an impact because they will advance our understanding of global influences on stroke recovery, and they will implicate GBH as a novel therapeutic target for potentiating recovery after stroke.

项目摘要 卒中后感觉运动恢复的神经生物学尚不完全了解。目前关于中风的研究 恢复重点是两个空间脑损伤水平：局灶性水平（即，病变和脑结构直接 受到中风的影响，例如皮质脊髓道）和网络水平（即，大脑结构远离 病变，但通过Diaschisis受影响）。该提议认为应考虑第三层：全球大脑 健康（GBH）定义为整个大脑的细胞，结构和血管完整性。虽然GBH 最近，在阿尔茨海默氏病和 创伤性脑损伤，其在中风恢复中的作用尚不清楚。同样，尽管焦点和网络 中风损伤的影响已经得到充分研究，对中风出口的全球影响范围知之甚少 整个大脑。这项研究的主要科学前提是（a）GBH调节整体神经塑性 促进中风恢复和（b）急性中风损伤的资源会导致全球大脑健康变化。这 中心假设是GBH差与中风结果不良有关，相反，严重的急性中风 伤害与担心GBH有关。拟议研究的基本原理是建立GBH 作为中风恢复的有意义的贡献者，可能会刺激研究的新途径和新的目标 治疗发展。 GBH将通过与大脑有关的四个脑成像指标估计为索引 健康（预测的大脑年龄反映结构性萎缩，深白质超强度的严重程度， 周期性高强度和血管周空间）。 AIM 1将利用大型回顾性中风 来自Enigma Stroke恢复工作组（n = 627）的神经影像学和行为数据库 表征GBH和中风结果之间的关系。 AIM 2将在三个星期内使用个人使用前瞻性，多站点的纵向数据收集（n = 144），并且 中风后三个月，研究最初的GBH与中风后脑修复和感觉运动如何相关 恢复。 AIM 3将使用相同的前瞻性数据集（n = 144）来检查急性中风的严重程度 与3周至3个月之间GBH的纵向变化有关。关于关键发现，我们期望 为了证明GBH与感觉运动结果有关，并预测了早期恢复的程度，并且 在这种情况下，GBH的演变。拟议的工作具有创新性，因为它打开了一个全新的框架 这是在中风后考虑感觉运动恢复的。结果预计会产生影响，因为他们 将促进我们对全球对中风恢复的影响的理解，他们将把GBH作为新颖 中风后潜在恢复的治疗靶标。