All projects will be supported by our High-Resolution Optical Imaging Core A (Boas/Sakadzic). This core will support the theme of functional coupling between glial, endothelial, and neuronal cells by using both in vivo and in vitro novel optical imaging to dissect the mechanisms of brain plasticity after cerebral ischemia . Novel optical imaging technologies have unique capability to measure the dynamics of glia, endothelium, and neurons as well as hemodynamic, metabolic, and electrophysiologic responses upon cerebral injury at the extensive range of temporal and spatial scales. Subcellular structures such as glial processes and neuronal spines will be assessed both in vivo and in vitro by Two-Photon Microscopy (TPM), and very fine subcellular interactions will be imaged by sub-diffraction-limit Stohastic Optical Reconstruction Microscopy (STORM). Optical Coherence Tomography (OCT) is unique in its ability to assess large cortical area and depth with high-resolution through a thin skull and it will be used to image longitudinally the recovery and remodeling of blood flow and vascular morphology after stroke in mice. These studies will be complemented by advanced intravascular and tissue oxygenation measurements by two-photon phosphorescence lifetime microscopy. Our core will also support the optogenetics studies of glial activation as well as the Optical Coherence Microscopy (OCM) - based whole brain imaging of cellular morphology and tractography. Various standard imaging technologies such as TPM imaging of calcium dynamics, Voltage-Sensitive Dye Imaging (VSDI), and multispectral and speckle imaging of hemodynamics will be supported too. All imaging procedures will be accompanied by the advanced data processing and modeling algorithms developed by our core. Investigators in projects 1-3 have a track record of productive collaborations with our core that resulted in numerous advances in the field and a multitude of joint publications over the last decade. This core will directly interact with all 3 projects to utilize advanced optical methods to study the coupling between glial, endothelial, and neuronal cells in response to ischemia.

Public Health Relevance

Cell-cell signaling in the neurovascular unit may underlie mechanisms of recovery after stroke and brain injury. This Core will provide high resolution optical imaging methods to investigate these mechanisms in all cell and animal models across all projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS055104-06A1
Application #
8663355
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$302,237
Indirect Cost
$128,397
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Xing, Changhong; Wang, Xiaoshu; Cheng, Chongjie et al. (2014) Neuronal production of lipocalin-2 as a help-me signal for glial activation. Stroke 45:2085-92
Terasaki, Y; Liu, Y; Hayakawa, K et al. (2014) Mechanisms of neurovascular dysfunction in acute ischemic brain. Curr Med Chem 21:2035-42
Sheng, Rui; Zhang, Tong-Tong; Felice, Valeria D et al. (2014) Preconditioning stimuli induce autophagy via sphingosine kinase 2 in mouse cortical neurons. J Biol Chem 289:20845-57
Miyamoto, Nobukazu; Pham, Loc-Duyen D; Seo, Ji Hae et al. (2014) Crosstalk between cerebral endothelium and oligodendrocyte. Cell Mol Life Sci 71:1055-66
Cha, Jong-Ho; Wee, Hee-Jun; Seo, Ji Hae et al. (2014) Prompt meningeal reconstruction mediated by oxygen-sensitive AKAP12 scaffolding protein after central nervous system injury. Nat Commun 5:4952
Ahn, Bum Ju; Le, Hoang; Shin, Min Wook et al. (2014) Ninjurin1 enhances the basal motility and transendothelial migration of immune cells by inducing protrusive membrane dynamics. J Biol Chem 289:21926-36
Arai, Ken (2014) Stroke literature synopses: basic science. Stroke 45:e201
Arai, Ken (2014) Stroke literature synopses: basic science. Stroke 45:e247-8

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