Correlation between extracellular glutamate release and neuronal cell death in an eleven vessel occlusion model in rat.
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.
Park
Eunkuk
E
Department of Biomedical Engineering, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Lee
Gi Ja
GJ
Choi
Samjin
S
Choi
Seok Keun
SK
Chae
Su Jin
SJ
Kang
Sung Wook
SW
Park
Hun-Kuk
HK
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D045604:Extracellular Fluid / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018698:Glutamic Acid