This proposal seeks to study a clinically important disease, hyponatremia (low sodium in blood), which can result in brain damage. This application seeks to study the pathogenesis of hyponatremic encephalopathy via a multidisciplinary approach, with a goal of elucidating a mechanism by which failure of various adaptive mechanisms can induce hyponatremic encephalopathy. The applicant proposes to use proton magnetic resonance imaging (MRI) of the brain in vivo to explore possible structural changes and phosphorus (31-P) nuclear magnetic resonance spectroscopy (MRS) to evaluate cerebral metabolism in vivo. Pathologic alterations will be confirmed by histological techniques and correlated with MRI/MRS results. Additionally, Ca+ +, Na+, and K+ transport will be determined in vitro using synaptosomes prepared from the brain cerebral cortex. The effects of hormones with established and putative effects on cerebral fluid homeostasis will also be evaluated both in vivo and in vitro to ascertain whether specific neuroendocrine factors are responsible for the female predilection to hyponatremic encephalopathy.