Ionic shifts represent the earliest recorded events during insults to the central nervous system. Massive derangements of K+, Na+, Ca2+ and pH are known to accompany brain ischemia, and spinal cord injury. Although similar phenomena may occur following head trauma, there have been few systematic studies of ion dynamics in experimental brain injury. An understanding of ion behavior is critical to concepts of management and therapy, particularly in view of the role of ions in secondary injury, and the requirement of normal ion gradients for growth and repair. In this project, a detailed investigation of ion dynamics will be performed in two rat models of cortical injury. Using ion-selective microelectrodes, and conventional chemical and electrophysiological techniques, ionic shifts will first be characterized in a graded contusion model. These studies will address the underlying mechanism of ionic derangements, their relation to theories of secondary injury, and their relevance to contemporary therapeutic strategies. The effects of methylprednisolone on the recovery of ion homeostasis will be emphasized. A similar analysis will be performed in a model of local cortical compression, focusing on the magnitude and rate of compression, and the effects of rapid decompression. In the last year, the factors which govern the severity of acidosis in brain injury will be investigated. These studies will examine the role of serum glucose in the generation of brain acidosis and the efficacy of systemic base administration in its alleviation. Final experiments will examine the role of extracellular acidosis in governing the responsiveness of injured brain to excitotoxins.