Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia.
OBJECTIVE
Glutamate receptor antagonists have failed clinical stroke trials and it has been proposed that the action of N-methyl D-aspartate receptors is necessary for neuronal survival. Thus, excitatory amino acid transporters (EAATs) might be a promising therapeutic target. The aim of this study was to investigate glial expression of EAATs following ischaemia.


RESULTS
Expression of EAAT1 (GLAST) and EAAT2 (Glt-1) in 24 cases of ischaemia was examined by immunohistochemistry. Cortical expression of both EAATs in the lesion decreased within 24 h (P < 0.01, each). Whereas EAAT1+ white matter cells increased 18-fold (P < 0.05) within 24 h in the lesion and remained elevated for months in adjacent (469-fold, P < 0.01) and remote areas (20-fold, P < 0.05), EAAT2+ white matter cells were equivalent in ischaemia and controls. In the first week after stroke mainly activated (ramified and amoeboid) microglia expressed EAAT1, whereas monocytic cells in perivascular spaces and foamy macrophages lacked EAAT1. After more than 1 week, predominantly reactive astrocytes expressed EAAT1.


CONCLUSIONS
Microglial EAAT1 expression is restricted to the early/intermediate stage of activation and blood-derived (perivascular) monocytes do not contribute to EAAT1+ cells following ischaemia. Whether a pharmacological increase in glial EAAT expression may compensate for loss of cortical EAAT expression and reduce neuronal damage following stroke requires investigation by further functional studies.
Beschorner
R
R
Institute of Brain Research, Eberhard-Karls-University, Tübingen, Germany. rudi.beschorner@med.uni-tuebingen.de
Simon
P
P
Schauer
N
N
Mittelbronn
M
M
Schluesener
H J
HJ
Trautmann
K
K
Dietz
K
K
Meyermann
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D018696:Neuroprotective Agents
D015415:Biomarkers; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; C493397:SLC1A2 protein, human; C493394:SLC1A3 protein, human