Effects of glutamate receptor agonist on extracellular glutamate dynamics during moderate cerebral ischemia

We performed real-time monitoring of the extracellular glutamate dynamics in the rat striatum in vivo using the microdialysis electrode technique, during an experimental penumbral condition of moderate global cerebral ischemia and activated glutamate receptors. The local cerebral blood flow (CBF) was measured with a laser-Doppler probe. One minute after bilateral common carotid artery occlusion (BCAO), CBF was reduced to approximately 60% of the pre-ischemic value and it remained at this level during the period of occlusion. After BCAO, a transient depolarization and a transient increase in extracellular glutamate concentration ([Glu]e) were seen. In other rats, 500 microM N-methyl-D-aspartate (NMDA) was locally micro-transfused for 30 min prior to BCAO. Upon induction of BCAO, an anoxic depolarization-like depolarization and a gradual increase in [Glu]e that continued over the duration of BCAO were seen. After BCAO was terminated, the direct current (DC) rapidly recovered to the basal level, while [Glu]e gradually decreased to the basal level. In rats that were locally micro-transfused with 500 microM Kainate prior to BCAO, DC and [Glu]e did not differ significantly from control. Pretreatment with MK-801 prior to NMDA treatment completely inhibited the NMDA-induced changes in DC and [Glu]e. Pretreatment with NBQX prior to NMDA treatment did not inhibit the NMDA-induced changes in DC and [Glu]e. Consequently, we found that activation of NMDA receptors by elevated [Glu]e exerts an important effect on [Glu]e dynamics in the spreading stroke region very early in the acute stage of cerebral ischemia in vivo.