The aim of this study was to define the effects of glutamate release on cell death in an eleven vessel rat occlusion model. Male Sprague-Dawley rats (250-350g) were used for the 11 vessel occlusion ischemic model, which was induced by a 5- and 10-min transient occlusion. During the surgical procedure, the extracellular glutamate concentration was measured in real-time using a microdialysis amperometirc biosensor with cerebral blood flow. In order to confirm neuronal cell death, brains were removed 72h after ischemia for the detection of the neuron-specific nuclear protein and cleaved caspase-3 levels, using double-immunofluorescence. A significant decrease in % cerebral blood flow was observed in both the 5- and 10-min 11 vessel occlusion models, while an increase in glutamate release was detected after the onset of ischemia that continued to rise during the ischemic period. However, a significantly higher level of glutamate release was observed in the 10-min ischemia group compared to the 5-min group. Unlike the small amount of brain damage in the 5-min group, the increased glutamate levels in the 10-min group resulted in ischemic cell death in the hippocampal region with the activation of cleaved caspase-3 and the inhibition of neuron-specific nuclear protein expression. This study suggests that the increased level of glutamate release induces apoptotic cell death in the 11 vessel occlusion ischemic model.
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