Previous studies have implicated the brainstem as playing an integral role in the development and recovery from the coma asociated with the metaboli encephalopathies. Oxygen consumption is decreased in these disorders, indicating an underlying alteration in cerebral energy metabolism. Previous experimental studies on energy metabolites in comatose animals have been equivocal due in some measure to the analysis of large brain samples. Such samples by necessity may contain contiguous non-affected tissue. We have recently obtained data in both ammoni-induced and hypoglycemic coma showing dramatic changes in energy metabolites which are localized to areas of the reticular activating system. Cells as close to the reticular formation as 1 mm were not affected. In this proposed study we will examine energy metabolism in highly discrete brain areas in two experimental models of secondary metabolic encephalopathy. The models will include coma induced by ammonia and hypoglycemia. Both net levels as well as turnover of metabolites will be assessed. In some selected instances, analysis will be repeated in single neurons from the reticular formation and cerebral cortex. The hypothesis we wish to test is that the reticular activating system can act in an adaptive fashion by shutting off the organism (coma) resulting in decreased energy demands. This enables the organism to attempt to recover its threatened energy reserves in a condition of decreased energy needs. Results from this study will provide data as to the mechanism of the metabolic comas, and the interaction between the reticular formation and the cortex.