Abstract

Experimental models will induce carefully controlled levels of brain hypoxia, quantitated by direct measurement of oxygen levels in the tissue microcirculation, followed by periods of reoxygenation. These models will include brain hypoxia induced by arterial hypoxia (decreased FiO2; a high flow hypoxia) and hemorrhagic hypotension with bilateral carotid occlusion (a low flow hypoxia). The mechanism(s) of cellular dysfunction and/or injury will be examined at both the cellular and molecular levels. Changes in extracellular levels of glutamate and dopamine will be continuously monitored by in vivo microdialysis. The brain tissue will be screened for multiple genes that may be altered in expression level as the results of the hypoxic/ischemic episodes and reoxygenation. This will be performed using the amplified antisense RNA (aRNA) technique, and genes selected for analysis will correspond to proteins that are implicated as key points in dopamine-glutamate interactions. The role of dopamine, and of dopamine and glutamate receptors on the number of cells undergoing apoptosis and/or necrotic cell death will also be determined by the TUNEL technique.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS031465-12
Application #
6661303
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Leblanc, Gabrielle G
Project Start
1992-07-01
Project End
2005-12-31
Budget Start
2003-09-01
Budget End
2005-12-31
Support Year
12
Fiscal Year
2003
Total Cost
$396,250
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Wilson, David F; Vinogradov, Sergei A; Schears, Gregory J et al. (2012) Monitoring cardiopulmonary function and progression toward shock: oxygen micro-sensor for peripheral tissue. Adv Exp Med Biol 737:221-7
Ceroni, Paola; Lebedev, Artem Y; Marchi, Enrico et al. (2011) Evaluation of phototoxicity of dendritic porphyrin-based phosphorescent oxygen probes: an in vitro study. Photochem Photobiol Sci 10:1056-65
Wilson, David F; Finikova, Olga S; Lebedev, Artem Y et al. (2011) Measuring oxygen in living tissue: intravascular, interstitial, and ""tissue"" oxygen measurements. Adv Exp Med Biol 701:53-9
Pirzadeh, Afsaneh; Schears, Gregory; Pastuszko, Peter et al. (2011) Effect of deep hypothermic circulatory arrest followed by low-flow cardiopulmonary bypass on brain metabolism in newborn piglets: comparison of pH-stat and *-stat management. Pediatr Crit Care Med 12:e79-86
El Beheiry, Mostafa H; Heximer, Scott P; Voigtlaender-Bolz, Julia et al. (2011) Metoprolol impairs resistance artery function in mice. J Appl Physiol 111:1125-33
Pirzadeh, A; Mammen, A; Kubin, J et al. (2011) Early regional response of apoptotic activity in newborn piglet brain following hypoxia and ischemia. Neurochem Res 36:83-92
Mammen, A; Kubin, J; Greeley, W J et al. (2011) Effect of hypoxia on expression of selected proteins involved in regulation of apoptotic activity in striatum of newborn piglets. Neurochem Res 36:746-53
Ragoonanan, Tenille E; Beattie, W Scott; Mazer, C David et al. (2009) Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology 111:988-1000
Lebedev, Artem Y; Cheprakov, Andrei V; Sakadzic, Sava et al. (2009) Dendritic phosphorescent probes for oxygen imaging in biological systems. ACS Appl Mater Interfaces 1:1292-304
Lahiri, S; Roy, A; Baby, S M et al. (2009) Carotid body sensory discharge and glomus cell HIF-1 alpha are regulated by a common oxygen sensor. Adv Exp Med Biol 645:87-94

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