Ischemic depression of neuronal activity: real time comparison between DC potential changes and alterations of ion and transmitter homeostasis

The initial phase of brain ischemia sets the scene for final functional disturbance and tissue damage. Important contributors in the course of early events are tissue depolarization and breakdown of ion and of transmitter homeostasis including transmitter-gated ion channel opening. To relate these events to the severity of cerebral blood flow (CBF) reduction, we used two ischemia models in cats: a global model produced complete ischemia and a focal model produced gradual reductions in the CBF. We employed ion-selective microelectrodes in combination with microdialysis/HPLC to detect direct current (DC) potential and extracellular calcium as well as amino acids and purine catabolites. Additionally, we used amperometric glutamate electrodes for rapid detection of glutamate. Most regions exhibited tissue depolarization and were, therefore, denominated as severely ischemic. An extracellular decrease in calcium and an increase in glutamate were associated with depolarization. The temporal pattern of changes differed among models and regions: the initial phase took less than 10 min in global but up to 30 min in focal ischemia. Since extracellular adenosine as a marker of ATP depletion exhibited similar temporal variability in the various regions, we suggest that minor, not easily detectable, perfusional and metabolic differences are responsible for major differences in the pathophysiology of the initial phase of brain ischemia.