抄録
In the brain, prior sublethal ischemia (preconditioning, PC) is known to produce ischemic tolerance of neurons to subsequent lethal ischemia. In addition, previous studies have revealed that the function of neuronal and/or astrocytic glutamate (Glu) transporters is reversed during ischemia, and the reversed uptake of Glu especially by astrocytic GLT-1 is involved in the marked elevation of extracellular Glu in the ischemic brain. This study aims at elucidating whether Glu released from astrocytes is responsible for the development of neuronal ischemic tolerance in astrocyte/neuron co-cultures. Brain ischemia was simulated by deprivation of both oxygen and glucose (OGD) from co-cultures. When the activation of NMDA receptors during PC was suppressed by treatment with AP5, PC-induced neuronal ischemic tolerance was significantly depressed. In contrast, exposure of co-cultures to NMDA instead of sublethal OGD (PC) produced ischemic tolerance of neurons. Interestingly, treatment of co-cultures with dihydrokainic acid (DHK), a specific blocker of astrocytic GLT-1, during PC resulted in the significant reduction in the PC-induced neuronal ischemic tolerance. These results suggested that the activation of NMDA receptors during PC was crucial to the development of PC-induced ischemic tolerance of neurons, and this activation was probably caused by the marked elevation of extracellular Glu resulting from the reversed uptake of Glu by astrocytic GLT-1. [Jpn J Physiol 54 Suppl:S157 (2004)]
