title: Chronic brain ischemia induces the expression of glial glutamate transporter EAAT2 in subcortical white matter.
abstract: Glutamate plays a central role in brain physiology and pathology. The involvement of excitatory amino acid transporters (EAATs) in neurodegenerative disorders including acute stroke has been widely studied, but little is known about the role of glial glutamate transporters in white matter injury after chronic cerebral hypoperfusion. The present study evaluated the expression of glial (EAAT1 and EAAT2) and neuronal (EAAT3) glutamate transporters in subcortical white matter and cortex, before and 3-28 days after the ligation of bilateral common carotid arteries (LBCCA) in rat brain. K-B staining showed a gradual increase of demyelination in white matter after ischemia, while there was no cortical involvement. Between 3 and 7 days after LBCCA, a significant increase in EAAT2 protein levels was observed in the ischemic brain and the number of EAAT2-positive cells also significantly increased both in the cortical and white matter lesions. EAAT2 was detected in glial-fibrillary acidic protein (GFAP)-positive astrocytes in both the cortex and white matter, but not in neuronal and oligodendroglial cells. EAAT1 was slightly elevated after ischemia only in the white matter, but EAAT3 was at almost similar levels both in the cortex and white matter after ischemia. A significant increase in EAAT2 expression level was also noted in the deep white matter of chronic human ischemic brain tissue compared to the control group. Our findings suggest important roles for up-regulated EAAT2 in chronic brain ischemia especially in the regulation of high-affinity of extracellular glutamate and minimization of white matter damage.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yatomi
authors.forename: R
authors.initials: R
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Shimura
authors.forename: N
authors.initials: N
authors.lastname: Miyamoto
authors.forename: K
authors.initials: K
authors.lastname: Yamashiro
authors.forename: M
authors.initials: M
authors.lastname: Takanashi
authors.forename: T
authors.initials: T
authors.lastname: Urabe
authors.forename: N
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003337:Corpus Callosum / Q000378:metabolism* / Q000473:pathology; D003711:Demyelinating Diseases / Q000150:complications / Q000378:metabolism; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis*; D050580:Excitatory Amino Acid Transporter 3 / Q000096:biosynthesis; D005260:Female; D050491:Glutamate Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C493397:SLC1A2 protein, human; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; C493392:Slc1a3 protein, rat