Supplement to Effects of global brain health on sensorimotor recovery after stroke

补充全球大脑健康对中风后感觉运动恢复的影响

• 批准号: 10386724
• 负责人: Sook-Lei Liew
• 金额: $ 8.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-07 至 2022-04-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386724
• 关键词: Affect; Age; Alzheimer' s Disease; Atrophic; Behavioral; Blood Vessels; Brain; Brain Injuries; Brain imaging; Cellular Structures; Corticospinal Tracts; Data; Data Collection; Data Set; Databases; Deterioration; Distant; Focal Brain Injuries; Global Change; Individual; Injury; Knowledge; Lesion; Link; Measures; Mission; Motor; Neurobiology; Neuronal Plasticity; Outcome; Population; Public Health; Recovery; Research; Resources; Role; Sensory; Severities; Site; Stroke; Structure; System; Traumatic Brain Injury; United States National Institutes of Health; White Matter Hyperintensity; Work; acute stroke; brain health; brain repair; chronic stroke; improved; indexing; innovation; neuroimaging; new therapeutic target; outcome prediction; post stroke; prospective; stroke outcome; stroke patient; stroke recovery; therapeutic development; 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.

项目概要 中风后感觉运动恢复的神经生物学尚未完全了解。 恢复集中于脑损伤的两个空间水平：局灶水平（即病变和大脑结构直接 受中风影响的区域，例如皮质脊髓束）和网络水平（即远离中风的大脑结构） 该提案认为应该考虑第三个层次：全球大脑。 健康（GBH），被定义为整个大脑的细胞、结构和血管的完整性。 最近被认为是阿尔茨海默氏病和 创伤性脑损伤，其在中风恢复中的作用尚不清楚。尽管局灶性和类似网络 中风损伤的影响已得到充分研究，但人们对中风如何在全球范围内产生影响知之甚少。 这项研究的关键科学前提是 (a) GBH 调节整体神经可塑性。 促进中风康复的资源和（b）急性中风损伤导致大脑健康的全球变化。 中心假设是，不良 GBH 与不良卒中结果相关，相反，严重急性卒中 损伤与 GBH 恶化有关 本研究的基本原理是建立 GBH。 作为中风康复的有意义的贡献者可能会激发新的研究途径和新的目标 GBH 的治疗进展将根据与大脑相关的四种大脑成像指标进行评估。 健康（反映结构性萎缩的预测大脑年龄、深部白质高信号的严重程度、 目标 1 将利用大的回顾性卒中。 来自 ENIGMA 中风恢复工作组 (N=627) 的神经影像和行为数据库 描述横断面慢性卒中人群中 GBH 和卒中结果之间的关系。 目标 2 将在三周内对个体进行前瞻性、多地点、纵向数据收集 (N=144)， 中风后三个月研究初始 GBH 与中风后大脑修复和感觉运动的关系 目标 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，我们预计主要发现。 表明 GBH 与感觉运动结果相关并预测早期中风恢复的程度，并且 GBH 是在这种背景下发展起来的，所提出的工作是创新的，因为它打开了一个全新的框架。 考虑中风后的感觉运动恢复，结果预计会产生影响，因为它们。 将增进我们对中风康复的全球影响的理解，并将 GBH 视为一种新颖的 促进中风后恢复的治疗目标。