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

项目摘要 中风后感觉运动恢复的神经生物学尚未完全了解。脑卒中研究现状 恢复集中于脑损伤的两个空间水平：病灶水平（即，病变和大脑结构直接 受中风影响，例如皮质脊髓束）和网络水平（即，大脑结构远离 病变，但通过神经连接不能影响）。这一提议认为，应该考虑第三个层次：全球大脑 健康（GBH），其被定义为整个大脑的细胞、结构和血管完整性。虽然GBH 最近被认为是阿尔茨海默病等疾病结果的关键预测因素， 创伤性脑损伤，其在中风恢复中的作用还没有得到很好的理解。同样，虽然重点和网络 中风损伤的影响已经得到了很好的研究，但对中风如何在全球范围内产生影响却知之甚少。 整个大脑。这项研究的关键科学前提是（a）GBH调节整体神经可塑性 促进中风恢复的资源和（B）急性中风损伤引起脑健康的全球变化。的 中心假设是，不良GBH与不良卒中结局相关，相反，严重急性卒中 损伤与GBH的恶化有关。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，可能会刺激新的研究途径和新的靶点， 治疗发展GBH将通过与脑功能相关的四项脑成像指标进行估计。 健康（反映结构性萎缩的预测脑年龄，深部白色物质高信号的严重程度， 室周高信号和血管周围间隙）。Aim 1将利用大的回顾性卒中 ENIGMA卒中恢复工作组的神经影像学和行为数据库（N=627）， 在一个横断面慢性卒中人群中描述GBH和卒中结局之间的关系。 目标2将在三周内对个体进行前瞻性、多中心、纵向数据收集（N=144）， 在中风后三个月，研究初始GBH与中风后脑修复和感觉运动的关系。 复苏目标3将使用相同的前瞻性数据集（N=144）来检查急性卒中的严重程度 与3周至3个月之间GBH的纵向变化有关。关于主要调查结果，我们预计 表明GBH与感觉运动结果相关，并可预测早期卒中恢复的程度， GBH就是在这种背景下发展起来的。拟议的工作是创新的，因为它开辟了一个全新的框架， 中风后的感觉运动恢复。预计结果将产生影响，因为它们 将促进我们对中风恢复的全球影响的理解，他们将暗示GBH是一部小说， 治疗靶点，用于增强中风后的恢复。

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.