Remodeling and recovery in the neurovascular unit

神经血管单位的概念指出，中风、脑损伤和变性的病理生理学不能作为纯粹的神经元现象来研究。相反，必须考虑所有神经元、神经胶质和血管区室的细胞之间的相互作用。我们的P01项目的第一个周期的重点是解剖神经血管单位疾病的急性机制。在这个更新中，我们现在建议看看神经血管单位如何进行修复和恢复。 项目1（Lo/Xing：小胶质细胞开关的胶质血管调节）研究了内皮和 星形胶质细胞不同地调节小胶质细胞的活化。小胶质细胞可以跨越从“好”到 “坏”。我们将测试这一假设，即在神经胶质血管界面的信号调节小胶质细胞开关 因为神经血管单位从最初的损伤过渡到修复。项目2（Arai/Huang： 白色物质损伤后的恢复）检查了脑内皮细胞和 少突胶质细胞前体细胞介导患病白色物质的重塑。这使我们能够扩展 神经血管单位的概念，了解如何白色物质恢复和重新连接。项目3 （Ayata/货车Leyen：中风后神经血管恢复的靶向ROCK）将询问rho激酶 系统可以是在治疗期间特定神经元和血管恢复终点的中枢信号传导系统。 中风恢复这个项目也是我们在翻译方面的尝试，因为它提供了一个潜在的治疗靶点 促进神经血管单位的修复所有项目之间都存在直接合作。所有研究均 由三个核心支持。Core A（Boas/Sakadzic）为体内和细胞成像提供了强大的工具。 Core B（Whalen）支持神经行为测定，用于评估所有动物模型的恢复情况。 项目Core C（Lo）是我们的计划协调核心，为所有协作提供基础设施 我们对我们高度整合的P01的下一阶段感到兴奋，它剖析了细胞-细胞的新机制， 当神经血管单位从初始损伤转变时，内皮、神经胶质和神经元系统中的信号传导 中风、脑损伤和退化后的恢复。

The concept of the neurovascular unit states that the pathophysiology of stroke, brain injury, and degeneration cannot be investigated as a purely neuronal phenomenon. Instead, interactions between cells from all neuronal, glial, and vascular compartments must be considered. The first cycle of our P01 program was focused on dissecting acute mechansims of disease in the neurovascular unit. In this renewal, we now propose to look at how the neurovascular unit undergoes repair and recovery. Project 1 (Lo/Xing: Gliovascular regulation of the microglial switch) examines how endothelium and astrocytes differentially regulate the activation of microglia. Microglia can span the range from "good" to "bad". We will test the hypothesis that signaling at the gliovascular interface regulates the microglial switch as the neurovascular unit transitions from initial injury into repair. Project 2 (Arai/Huang: Mechanisms of recovery after white matter injury) examines how oligovascular signaling between brain endothelium and oligodendrocyte precursor cells mediate remodeling in diseased white matter. This allows us to extend the neurovascular unit concept for understanding how white matter recovers and reconnects. Project 3 (Ayata/van Leyen: Targeting ROCK for neurovascular recovery after stroke) will ask how the rho-kinase system may be a central signaling system for specific neuronal and vascular recovery endpoints during stroke recovery. This project is also our attempt at translation since it provides a potential therapeutic target for promoting neurovascular unit repair. Direct collaborations exist between all projects. All studies are supported by three cores. Core A (Boas/Sakadzic) provides powerful tools for in vivo and cellular imaging. Core B (Whalen) supports neuro-behavioral assays for assessing recovery in animal models across all projects. Core C (Lo) is our program coordination core that provides infrastructure for all collaborations We are excited about this next phase of our highly integrated P01 that dissects new mechanisms of cell-cell signaling in endothelial, glial and neuronal systems as the neurovascular unit transitions from initial injury into recovery after stroke, brain injury and degeneration.