title: Cerebral ischemic preconditioning reduces glutamate excitotoxicity by up-regulating the uptake activity of GLT-1 in rats.
abstract: Our previous study has shown that cerebral ischemic preconditioning (CIP) can up-regulate the expression of glial glutamate transporter-1 (GLT-1) during the induction of brain ischemic tolerance in rats. The present study was undertaken to further explore the uptake activity of GLT-1 in the process by observing the changes in the concentration of extracellular glutamate with cerebral microdialysis and high-performance liquid chromatography. The results showed that a significant pulse of glutamate concentration reached the peak value of sevenfold of the basal level after lethal ischemic insult, which was associated with delayed neuronal death in the CA1 hippocampus. When the rats were pretreated 2 days before the lethal ischemic insult with CIP which protected the pyramidal neurons against delayed neuronal death, the peak value of glutamate concentration decreased to 3.9 fold of the basal level. Furthermore, pre-administration of dihydrokainate, an inhibitor of GLT-1, prevented the protective effect of CIP on ischemia-induced CA1 cell death. At the same time, compared with the CIP + Ischemia group, the peak value of glutamate concentration significantly increased and reached sixfold of the basal level. These results indicate that CIP induced brain ischemic tolerance via up-regulating GLT-1 uptake activity for glutamate and then decreasing the excitotoxicity of glutamate.
authors.affiliation: Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
authors.forename: Jianxue
authors.initials: J
authors.lastname: Gong
authors.forename: Shujuan
authors.initials: S
authors.lastname: Gong
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Lianwei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Hu
authors.forename: Yixian
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D019194:Ischemic Preconditioning; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid; C020889:dihydrokainic acid; D007608:Kainic Acid