Deciphering the complex metabolic and molecular basis of cerebral ischemia and using this knowledge to develop therapeutic strategies for stroke treatment and rehabilitation is the theme of this competitive renewal application from the Interdepartment Stroke Program Project at the MGH. To this end, three (3) projects, plus one (1) Scientific and one (1) Administrative Core are proposed. Project 1 (Michael Moskowitz) continues to explore the role of nitric oxide in the cerebrovasculature and will expand preliminary data describing the therapeutic merits of eNOS up-regulation in wild type and in endothelial NOS knockout mice using a novel treatment strategy, chronic HMG-CoA reductase inhibition. Project 2 (Joseph Bonventre) will examine and characterize the importance of phospholipase A2 in normal and ischemic brain using recently cPLA2-/- mice. TO this end, he will evaluate in vivo the mechanisms of protection documented in this mutant mouse, and the role of cPLA2 in excitotoxic brain damage. Additional studies will explore the importance of cPLA2 interacting protein (PLIP) and evaluate the role of this protein in neuronal injury and glutamate release. Project 3 (Seth Finklestein) will continue to explore the importance of basic FGF on stroke recovery. These studies will be the first to extend the Stroke Program Project to investigate recovery of function, particularly as it relates to new neuronal sprouting and synap formation in the ischemic brain. Each of the projects will utilize the Scientific-Imaging Core (Bruce Rosen, Bradley Hyman) using state-of-the-art techniques in MR and morphometry. The approach taken is multi-disciplinary, interdepartmental, represents a logical extension of work accomplished during the previous funding period, incorporates new and exciting developments in molecular biology and genetics, introduces young promising scientists to the field of stroke (Drs. Liao, Hyman) and incorporates state-of-the-art imaging tools to examine the consequences of ischemia on brain metabolism, blood flow, tissue survival and recovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
2P50NS010828-24
Application #
2828725
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Jacobs, Tom P
Project Start
1977-02-01
Project End
2004-04-30
Budget Start
1999-07-15
Budget End
2000-04-30
Support Year
24
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Yaseen, Mohammad A; Srinivasan, Vivek J; Gorczynska, Iwona et al. (2015) Multimodal optical imaging system for in vivo investigation of cerebral oxygen delivery and energy metabolism. Biomed Opt Express 6:4994-5007
Miao, Yanying; Liao, James K (2014) Potential serum biomarkers in the pathophysiological processes of stroke. Expert Rev Neurother 14:173-85
Sawada, Naoki; Liao, James K (2014) Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in atherosclerosis. Antioxid Redox Signal 20:1251-67
Hayakawa, Kazuhide; Miyamoto, Nobukazu; Seo, Ji Hae et al. (2013) High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter. J Neurochem 125:273-80
Tanaka, Shin-ichi; Fukumoto, Yoshihiro; Nochioka, Kotaro et al. (2013) Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation. Arterioscler Thromb Vasc Biol 33:1591-600
Montalvo, J; Spencer, C; Hackathorn, A et al. (2013) ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression. Curr Mol Med 13:205-19
Yaseen, Mohammad A; Sakadži?, Sava; Wu, Weicheng et al. (2013) In vivo imaging of cerebral energy metabolism with two-photon fluorescence lifetime microscopy of NADH. Biomed Opt Express 4:307-21
Zhou, Qian; Mei, Yu; Shoji, Takuhito et al. (2012) Rho-associated coiled-coil-containing kinase 2 deficiency in bone marrow-derived cells leads to increased cholesterol efflux and decreased atherosclerosis. Circulation 126:2236-47
Sakadži?, Sava; Roussakis, Emmanuel; Yaseen, Mohammad A et al. (2011) Cerebral blood oxygenation measurement based on oxygen-dependent quenching of phosphorescence. J Vis Exp :
Yaseen, Mohammad A; Srinivasan, Vivek J; Sakadzic, Sava et al. (2011) Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation. J Cereb Blood Flow Metab 31:1051-63

Showing the most recent 10 out of 128 publications