DOPAMINE/GLUTAMATE AND HYPOXIC INJURY IN NEWBORN BRAIN

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DESCRIPTION: (Adapted from the Investigator's 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.