Abstract
Excessively released glutamate is neurotoxic. Glutamate transporters maintain the extracellular level of glutamate by uptake into glia or neurons. We examined the role of GLT-1, a glial glutamate transporter, in brain damage resulting from transient focal ischemia in mice. Heterozygous gene deletion of GLT-1 significantly augmented brain swelling resulting from 1 h of middle cerebral artery occlusion and 24 h reperfusion. In addition, this gene deletion significantly increased brain water contents in ischemic hemisphere at 6 h after reperfusion. Moreover, intraperitoneal injection of dihydrokainate (10 mg/kg), a specific inhibitor of GLT-1, augmented brain swelling. These data suggest that GLT-1 limits brain edema resulting from ischemia.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / drug effects
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Brain / metabolism
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Brain / physiopathology
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Brain Edema / genetics*
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Brain Edema / metabolism*
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Brain Edema / physiopathology
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Brain Ischemia / complications*
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Excitatory Amino Acid Transporter 2 / antagonists & inhibitors
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Excitatory Amino Acid Transporter 2 / deficiency*
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Excitatory Amino Acid Transporter 2 / genetics
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Extracellular Space / metabolism
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Female
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Glutamic Acid / metabolism*
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Infarction, Middle Cerebral Artery / complications
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Kainic Acid / analogs & derivatives*
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Kainic Acid / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neuroglia / metabolism*
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Neurotoxins / metabolism
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Neurotransmitter Uptake Inhibitors / pharmacology
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Reperfusion Injury / complications*
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Water-Electrolyte Balance / genetics
Substances
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Excitatory Amino Acid Transporter 2
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Neurotoxins
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Neurotransmitter Uptake Inhibitors
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Glutamic Acid
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dihydrokainic acid
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Kainic Acid