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.
Mechanisms of remodeling and repair studied here should allow us to find ways to promote recovery after stroke. Our overall goal fits with the NINDS Stroke Progress Review which identified remodeling in the neurovascular unit as a high priority area. Importantly, the mechanisms dissected here have relevance not just for stroke but more broadly for brain injury and neurodegeneration as well.
|Kura, Sreekanth; Xie, Hongyu; Fu, Buyin et al. (2018) Intrinsic optical signal imaging of the blood volume changes is sufficient for mapping the resting state functional connectivity in the rodent cortex. J Neural Eng 15:035003|
|Sadeghian, Homa; Lacoste, Baptiste; Qin, Tao et al. (2018) Spreading depolarizations trigger caveolin-1-dependent endothelial transcytosis. Ann Neurol 84:409-423|
|Chung, David Y; Sadeghian, Homa; Qin, Tao et al. (2018) Determinants of Optogenetic Cortical Spreading Depolarizations. Cereb Cortex :|
|Takase, Hajime; Liang, Anna C; Miyamoto, Nobukazu et al. (2018) Protective effects of a radical scavenger edaravone on oligodendrocyte precursor cells against oxidative stress. Neurosci Lett 668:120-125|
|Maki, Takakuni; Choi, Yoon Kyung; Miyamoto, Nobukazu et al. (2018) A-Kinase Anchor Protein 12 Is Required for Oligodendrocyte Differentiation in Adult White Matter. Stem Cells 36:751-760|
|Tang, Jianbo; Erdener, Sefik Evren; Li, Baoqiang et al. (2018) Shear-induced diffusion of red blood cells measured with dynamic light scattering-optical coherence tomography. J Biophotonics 11:|
|Chung, David Y; Sugimoto, Kazutaka; Fischer, Paul et al. (2018) Real-time non-invasive in vivo visible light detection of cortical spreading depolarizations in mice. J Neurosci Methods 309:143-146|
|Gómez, Carlos A; Sutin, Jason; Wu, Weicheng et al. (2018) Phasor analysis of NADH FLIM identifies pharmacological disruptions to mitochondrial metabolic processes in the rodent cerebral cortex. PLoS One 13:e0194578|
|Maki, Takakuni; Morancho, Anna; Martinez-San Segundo, Pablo et al. (2018) Endothelial Progenitor Cell Secretome and Oligovascular Repair in a Mouse Model of Prolonged Cerebral Hypoperfusion. Stroke 49:1003-1010|
|Wang, Hui; Magnain, Caroline; Wang, Ruopeng et al. (2018) as-PSOCT: Volumetric microscopic imaging of human brain architecture and connectivity. Neuroimage 165:56-68|
Showing the most recent 10 out of 240 publications