The objective of the Cerebral Vascular Disease Research Center at the University of Miami is to carry out an integrated, multi-disciplinary program of experimental research into the mechanisms and therapies of ischemic brain injury. The overall goal of our research program is to identify and characterize those factors responsible for engendering ischemic injury that may be amenable to therapeutic or prophylactic intervention. The Program Project consists of three investigative proposals supported by General-Scientific and Image- Analysis/Computing Core facilities. Project areas include 1) focal cerebral ischemia: a study of the mechanisms of neuroprotection underlying human serum albumin therapy, and of exacerbation of injury due to hyperthermia (fever); 2) mitochondria and cerebral anoxia/ischemia: basic mechanistic studies of protection and dysfunction; and 3) the metabolic and structural consequences of evolving mitochondrial and ionic dysfunction in focal ischemia. The projects are closely integrated with one another, both conceptually and methodologically, and are strongly supported by close collaborative interactions among the investigators and research personnel. The core facilities contribute substantively to the implementation of each project and unify the overall program by common methodological approaches. The General Scientific Core compromises animal physiology; methods of focal and global cerebral ischemia; neurobehavioral strategies; morphological methods including quantitative light microscopy and stereology; immunohistochemistry, confocal microscopy; autoradiographic strategies for local cerebral blood flow and glucose utilization; enzymatic tissue sampling and metabolic analyses; and molecular biological methods, including in situ hybridization, Northern and Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR). The Image-Analysis and Computing Core has pioneered in the development of three-dimensional autoradiographic image-averaging and is a central resource supporting image-analysis of autoradiographic, molecular biological, and histopathological data; as well as acquisition, statistical analysis and archiving of laboratory data, instrumentation control, and data base management.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS005820-36
Application #
6393231
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Jacobs, Tom P
Project Start
1976-08-01
Project End
2005-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
36
Fiscal Year
2001
Total Cost
$1,290,318
Indirect Cost
Name
University of Miami School of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
Dave, Kunjan R; Della-Morte, David; Saul, Isabel et al. (2013) Ventricular fibrillation-induced cardiac arrest in the rat as a model of global cerebral ischemia. Transl Stroke Res 4:571-8
Della-Morte, D; Raval, A P; Dave, K R et al. (2011) Post-ischemic activation of protein kinase C ? protects the hippocampus from cerebral ischemic injury via alterations in cerebral blood flow. Neurosci Lett 487:158-62
Dave, Kunjan R; Anthony Defazio, Richard; Raval, Ami P et al. (2009) Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel. J Neurochem 110:1170-9
DeFazio, R Anthony; Raval, Ami P; Lin, Hung W et al. (2009) GABA synapses mediate neuroprotection after ischemic and epsilonPKC preconditioning in rat hippocampal slice cultures. J Cereb Blood Flow Metab 29:375-84
Della-Morte, D; Dave, K R; DeFazio, R A et al. (2009) Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway. Neuroscience 159:993-1002
Park, Hee-Pyoung; Nimmagadda, Anitha; DeFazio, Richard A et al. (2008) Albumin therapy augments the effect of thrombolysis on local vascular dynamics in a rat model of arteriolar thrombosis: a two-photon laser-scanning microscopy study. Stroke 39:1556-62
Dave, Kunjan R; DeFazio, R Anthony; Raval, Ami P et al. (2008) Ischemic preconditioning targets the respiration of synaptic mitochondria via protein kinase C epsilon. J Neurosci 28:4172-82
Kim, Eun J; Raval, Ami P; Perez-Pinzon, Miguel A (2008) Preconditioning mediated by sublethal oxygen-glucose deprivation-induced cyclooxygenase-2 expression via the signal transducers and activators of transcription 3 phosphorylation. J Cereb Blood Flow Metab 28:1329-40
Nimmagadda, Anitha; Park, Hee-Pyoung; Prado, Ricardo et al. (2008) Albumin therapy improves local vascular dynamics in a rat model of primary microvascular thrombosis: a two-photon laser-scanning microscopy study. Stroke 39:198-204
Kim, E; Raval, A P; Defazio, R A et al. (2007) Ischemic preconditioning via epsilon protein kinase C activation requires cyclooxygenase-2 activation in vitro. Neuroscience 145:931-41

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