Cytotoxic brain edema is a serious complication of several clinical conditions including stroke, liver failure and traumatic brain injury and is characterized by swelling of astrocytes while volumes of neurons and other cells are relatively unaffected. It has been established that cell volume regulation in isolated astrocytes and neurons depends to some extent on the synthesis and transport of taurine. The central hypothesis of the application is that taurine is transported from neurons to astroglial cells during the development of cytotoxic brain edema, a process of regulation of neuronal volume. Based upon this hypothesis, it is proposed: (1) to determine swelling-induced changes in cell volume and taurine content of neurons and glia in hippocampal slices; (2) to test the proposal that taurine efflux from neurons is more sensitive and is distinct from that from astrocytes; (3) to characterize signal transduction pathways involved in taurine efflux in neurons versus astrocytes; (4) to examine volume regulation, electrophysiology and ion homeostasis in hippocampal slices exposed to osmotic edema. It is suggested that these studies will provide a better understanding of mechanisms of brain cell volume regulation under physiological conditions and the response of brain cells to pathological swelling, the knowledge of which will help in understanding cytotoxic brain edema in clinical states and in developing novel therapies.
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