Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2, reflecting a neuroprotective potential following ischaemia

R. Beschorner*, P. Simon, N. Schauer, M. Mittelbronn, H. J. Schluesener, K. Trautmann, K. Dietz, R. Meyermann

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

55 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)897-910
Number of pages14
JournalHistopathology
Volume50
Issue number7
DOIs
Publication statusPublished - Jun 2007
Externally publishedYes

Keywords

  • Excitatory amino acid transporters
  • Focal cerebral ischaemia
  • Glial glutamate transporters
  • Neuroprotection
  • Stroke

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