Remodeling and recovery in the neurovascular unit

神经血管单位的概念表明，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。取而代之的是，必须考虑来自所有神经元、神经胶质和血管隔室的细胞之间的相互作用。我们P01计划的第一个周期专注于解剖神经血管单位的急性疾病机制。在这次更新中，我们现在建议看看神经血管单位是如何进行修复和恢复的。 项目1(LO/XING：小胶质细胞开关的胶质血管调节)研究了内皮细胞和 星形胶质细胞对小胶质细胞的激活有不同的调节作用。小胶质细胞的范围从“好”到 “坏”。我们将检验在神经胶质血管界面上的信号调节小胶质细胞开关的假设。 随着神经血管单位从最初的损伤过渡到修复。项目2(ARAI/Huang：机制 脑白质损伤后的恢复)检查了脑内皮细胞和脑组织之间的少血管信号转导 少突胶质前体细胞参与病变白质的重塑。这使我们可以扩展 神经血管单位概念，用于了解白质如何恢复和重新连接。项目3 (Ayata/van Leyen：中风后神经血管恢复的靶向ROCK)将询问Rho-Kinase如何 系统可能是特定神经元和血管恢复端点的中枢信号系统 中风恢复了。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目标 用于促进神经血管单位的修复。所有项目之间存在直接协作。所有的研究都是 由三个内核支持。核心A(Boas/Sakadzic)为活体和细胞成像提供了强大的工具。 CORE B(惠伦)支持神经行为分析，用于评估所有动物模型的恢复情况 项目。核心C(LO)是我们的计划协调核心，为所有协作提供基础设施 我们对我们高度集成的P01的下一阶段感到兴奋，它剖析了细胞-细胞的新机制 随着神经血管单位从最初的损伤转变，内皮、神经胶质和神经系统中的信号转导 中风、脑损伤和变性后的康复。

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.