title: Inhibition of glial glutamate transporter GLT-1 augments brain edema after transient focal cerebral ischemia in mice.
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.
authors: Stroke and Brain Protection, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan. namura@ri.ncvc.go.jp
authors: Shobu
authors: S
authors: Namura
authors: Hiroshi
authors: H
authors: Maeno
authors: Shinya
authors: S
authors: Takami
authors: Xiao-Fan
authors: XF
authors: Jiang
authors: Sally
authors: S
authors: Kamichi
authors: Keiji
authors: K
authors: Wada
authors: Izumi
authors: I
authors: Nagata
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications*; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D015427:Reperfusion Injury / Q000150:complications*; D014882:Water-Electrolyte Balance / Q000235:genetics
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D009498:Neurotoxins; D014179:Neurotransmitter Uptake Inhibitors; D018698:Glutamic Acid; C020889:dihydrokainic acid; D007608:Kainic Acid