Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 31, Issue 5, Pages 1283-1292Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2010.222
Keywords
focal brain ischemia; glutamate transporter; ischemic tolerance; mouse; oxidative stress
Categories
Funding
- National Institutes of Health, Bethesda, Maryland, USA [R01 GM065211]
- International Anesthesia Research Society
- Department of Anesthesiology, University of Virginia
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Excitatory amino-acid transporters (EAATs) transport glutamate into cells under physiologic conditions. Excitatory amino-acid transporter type 3 (EAAT3) is the major neuronal EAAT and also uptakes cysteine, the rate-limiting substrate for synthesis of glutathione. Thus, we hypothesize that EAAT3 contributes to providing brain ischemic tolerance. Male 8-week-old EAAT3 knockout mice on CD-1 mouse gene background and wild-type CD-1 mice were subjected to right middle cerebral artery occlusion for 90 minutes. Their brain infarct volumes, neurologic functions, and brain levels of glutathione, nitrotyrosine, and 4-hydroxy-2-nonenal (HNE) were evaluated. The EAAT3 knockout mice had bigger brain infarct volumes and worse neurologic deficit scores and motor coordination functions than did wild-type mice, no matter whether these neurologic outcome parameters were evaluated at 24 hours or at 4 weeks after brain ischemia. The EAAT3 knockout mice contained higher levels of HNE in the ischemic penumbral cortex and in the nonischemic cerebral cortex than did wild-type mice. Glutathione levels in the ischemic and nonischemic cortices of EAAT3 knockout mice tended to be lower than those of wild-type mice. Our results suggest that EAAT3 is important in limiting ischemic brain injury after focal brain ischemia. This effect may involve attenuating brain oxidative stress. Journal of Cerebral Blood Flow & Metabolism(2011) 31, 1283-1292; doi:10.1038/jcbfm.2010.222; published online 8 December 2010
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