The upregulation of glial glutamate transporter-1 participates in the induction of brain ischemic tolerance in rats.
Glial glutamate transporter-1 (GLT-1) plays an essential role in removing glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), the present study was undertaken to observe in vivo changes in the expression of GLT-1 and glial fibrillary acidic protein (GFAP) in the CA1 hippocampus during the induction of BIT, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of BIT in rats. Immunohistochemistry for GFAP showed that the processes of astrocytes were prolonged after a CIP 2 days before the lethal ischemic insult, which could protect pyramidal neurons in the CA1 hippocampus against delayed neuronal death induced normally by lethal ischemic insult. The prolonged processes extended into the area between the pyramidal neurons and tightly surrounded them. These changes made the pyramidal layer look like a 'shape grid'. Simultaneously, the prolonged and extended processes showed a great deal of GLT-1. Western blotting analysis showed significant upregulation of GLT-1 expression after the CIP, especially when it was administered 2 days before the subsequent lethal ischemic insult. Neuropathological evaluation by thionin staining showed that DHK dose-dependently blocked the protective role of CIP against delayed neuronal death induced normally by lethal brain ischemia. It might be concluded that the surrounding of pyramidal neurons by astrocytes and upregulation of GLT-1 induced by CIP played an important role in the acquisition of the BIT induced by CIP.
Zhang
Min
M
Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, PR China.
Li
Wen-Bin
WB
Geng
Jin-Xia
JX
Li
Qing-Jun
QJ
Sun
Xiao-Cai
XC
Xian
Xiao-Hui
XH
Qi
Jie
J
Li
Shu-Qin
SQ
D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; C020889:dihydrokainic acid; D007608:Kainic Acid