description): The overall program hypothesis is that oxygen deprivation leads to alterations in cytosolic, membrane and nuclear events that form the underlying basis for cellular adaptation, sublethal injury or cell death. The extent of these alterations depends on many factors including age, type of cell and its endowments in both excitable (e.g. neurons) and non-excitable cells (e.g. glia, renal tubular epithelium), and severity and chronicity of hypoxia. The central aims of this program are therefore to: 1) define the nature of the response to hypoxia in neurons, glia and renal tubular epithelium in mature and immature cells; and 2) delineate the underlying mechanisms at the cellular and molecular level. To address these aims and determine the mechanisms that can lead to injury or adaptation and survival in the mature and immature cell, four projects and three cores are proposed. To accomplish these aims, the investigators will use state-of-the-art techniques and methodologies including electrophysiologic methods, electron, immunofluorescent, confocal and video-microscopy, Nuclear Magnetic Resonance, and molecular biologic techniques to study native tissue, tissue slices, dissociated and cultured cells.
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