title: The role of glutamate transporter-1a in the induction of brain ischemic tolerance in rats.
abstract: This study was undertaken to determine the role of glutamate transporter-1a (GLT-1a), one of the splice variants of glutamate transporter-1, in the induction of brain ischemic tolerance by cerebral ischemic preconditioning (CIP). We used a rat global cerebral ischemic model and assessed changes by neuropathological evaluation, Western blot analysis, immunohistochemistry, real-time PCR, in vivo brain microdialysis, and high performance liquid chromatography. We found that CIP induced a significant upregulation of GLT-1a expression in the CA1 hippocampus in a time course corresponding to that of neuroprotection of CIP against brain ischemia. Severe brain ischemia for 8 min induced delayed downregulation of GLT-1a, an obvious increase in glutamate concentration and delayed neuronal death of the pyramidal neurons in the CA1 hippocampus. When the animals were pretreated with CIP before the severe ischemia, the above changes normally induced by the severe ischemia were effectively prevented. Importantly, such a preventive effect of CIP on these changes was significantly inhibited by intracerebroventricular administration of GLT-1a antisense oligodeoxynucleotides, which have been proven to specifically inhibit the expression of GLT-1a protein and mRNA, and had no effect on the expression of GLT-1b. In addition, the concentration of aspartate was also elevated after severe brain ischemic insult. However, CIP had no effect on the elevated aspartate concentrations. These results indicate that GLT-1a participated in the brain ischemic tolerance induced by CIP in rats.
authors.affiliation: Department of Pathophysiology, Hebei Medical University, Shijiazhuang, People's Republic of China.
authors.forename: Yi-Xian
authors.initials: YX
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Li-Zhe
authors.initials: LZ
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Hu
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Li
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D056547:CA1 Region, Hippocampal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D017551:Microdialysis; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000596:Amino Acids; D027342:Excitatory Amino Acid Transporter 2; D020319:Oligodeoxyribonucleotides, Antisense