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Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia
Author(s) -
Beschorner R,
Simon P,
Schauer N,
Mittelbronn M,
Schluesener H J,
Trautmann K,
Dietz K,
Meyermann R
Publication year - 2007
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2007.02703.x
Subject(s) - microglia , neuroprotection , ischemia , glutamate receptor , biology , lesion , astrocyte , neuroglia , receptor , white matter , pathology , medicine , inflammation , neuroscience , immunology , central nervous system , biochemistry , radiology , magnetic resonance imaging
Aims: 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. Methods and 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.