The central nervous system functions in an environment that is well regulated in respect to its acid-base and electrolyte constituents. Small changes in these constituents can be associated with altered brain function. The objectives of this research are to understand and interrelate brain acid-base and fluid and electrolyte regulation, metabolism and brain function as evaluated by the control of breathing in both newborns and adults. The general approach is based on the hypothesis that mechanisms in brain tissue ( including neurons, glia, and choroid plexus) and at the blood-brain barrier are involved in brain environmental regulation. Cerebrospinal fluid (CSF) and brain tissue will be studied in certain specific stresses. In acid-base disturbances the relative roles and importance of brain tissue mechanisms that respond to PCO2 and blood-brain barrier mechanisms that govern the HCO3 ion distribution between blood and brain will be evaluated. In osmotic sress brain cell volume is protected. Whether the regulatory processes involved in this protection alter acid-base balance and/or the control of breathing will be studied in adult rats, newborn puppies and in the euryhaline species Squalus acanthias and Raja erinacea. With chronic potassium depletion CSF acid-base regulation and the control of the breathing pattern are altered. The mechanisms and possible interrelations of these effects will be examined in potassium depleted rats. Asphyxia adversely affects brain acid-base and electrolyte regulation and function in adults. Newborn mammals and certain vertebrates e.g., seal, beaver and turtle, have greater asphyxial tolerance. Whether this tolerance includes special and/or more effective mechanisms of brain acid-base and electrolyte regulation will be examined. Finally, the role of individual brain cell types, neurons or gila, in response to acid-base and osmotic stress will be evaluated in vitro using transformed cell lines grown in tissue culture.