Inhibition of glial glutamate transporter GLT-1 augments brain edema after transient focal cerebral ischemia in mice.
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.
Namura
Shobu
S
Stroke and Brain Protection, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan. namura@ri.ncvc.go.jp
Maeno
Hiroshi
H
Takami
Shinya
S
Jiang
Xiao-Fan
XF
Kamichi
Sally
S
Wada
Keiji
K
Nagata
Izumi
I
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
D027342:Excitatory Amino Acid Transporter 2; D009498:Neurotoxins; D014179:Neurotransmitter Uptake Inhibitors; D018698:Glutamic Acid; C020889:dihydrokainic acid; D007608:Kainic Acid