Voltage-dependent anion channel (VDAC) is the main
protein in mitochondria-mediated apoptosis, and the modulation of VDAC may be induced by the excessive release of extracellular
glutamate. This study examined the role of
glutamate release on VDAC-mediated apoptosis in an eleven vessel occlusion model in rats. Male Sprague-Dawley rats (250-350 g) were used for the 11 vessel occlusion ischemic model, which were induced for a 10-min transient occlusion. During the ischemic and initial reperfusion episode, the real-time monitoring of the extracellular
glutamate concentration was measured using an amperometric microdialysis biosensor and the cerebral blood flow (CBF) was monitored by
laser-Doppler flowmetry. To confirm neuronal apoptosis, the brains were removed 72 h after
ischemia to detect the neuron-specific
nuclear protein and
pro-apoptotic proteins (cleaved
caspase-3, VDAC, p53 and BAX). The changes in the mitochondrial morphology were measured by atomic force microscopy. A decrease in the % of CBF was observed, and an increase in
glutamate release was detected after the onset of
ischemia, which continued to increase during the ischemic period. A significantly higher level of
glutamate release was observed in the
ischemia group. The increased
glutamate levels in the
ischemia group resulted in the activation of VDAC and
pro-apoptotic proteins in the hippocampus with morphological alterations to the mitochondria. This study suggests that an increase in
glutamate release promotes VDAC-mediated apoptosis in an 11 vessel occlusion ischemic model.