Background
In cerebral thromboembolic stroke, decreased cerebral blood flow leads to a critical disturbance of energy supply. Although pathophysiologic changes have been observed in focal cerebral ischemia models in which the middle cerebral artery was occluded with artificial materials, few studies of the cerebral metabolic rate of glucose (CMRglc) in the ultra-acute stage of thromboembolic stroke models have been published. Free radicals are involved in various processes of damage in ischemic brain tissue, and edaravone is a widely known free radical scavenger, which is licensed in Japan and used for therapy in the acute phase of human stroke. Therefore, the aim of this study was to investigate whether elevated glucose uptake after thromboembolic stroke correlates with the process of brain tissue damage, and to determine whether edaravone affects elevated glucose uptake.
Methods and Results
Thromboembolic stroke was produced in male cynomolgus monkeys (n=8). Permanent obstruction of the left middle cerebral artery was achieved by injecting an autologous blood clot via the left internal carotid artery. PET studies were performed using microPET Primate 4 (Concorde Microsystems Inc., Knoxville, TN). 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) was administered intravenously at 2 mCi/kg and CMRglc was measured before embolization, and at 6 and 24 hours after embolization. Edaravone was injected at a rate of 1 mg/kg/hr for 3 h from 1 h after embolization. At 6 hours after stroke, increased 18F-FDG accumulation (1.4 times) was noted in the parietal and temporal cortices in all cases, while CMRglc in the insular cortex and basal ganglia, regarded as the ischemic core region, decreased to <70% of the pre-values. However, regions in which hyper-accumulation of 18F-FDG is observed, changed to loss of FDG hot spot after 24 hours of embolization. In histological analysis, these regions of changed FDG accumulation were almost completely infarcted area by 24 hours after embolization. Conversely, in the edaravone-treated group, increased 18F-FDG accumulation was maintained at > 90% of the pre-values in the parietal and temporal cortexes and thalamus, but not in the putamen or insular cortex, at 24 hours after embolization.
Conclusion
The results of the present study demonstrate that increased 18F-FDG accumulation around lesions in the ultra-acute stage of cerebral ischemic stroke is closely associated with infarct volume in the late stage. However, edaravone has a beneficial effect on decreased 18F-FDG uptake in the area around the ischemic core. Consequently, it may be postulated that this mechanism is involved in free radical generation resulting from ischemia.