Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury

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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

53 Citations (Scopus)

Abstract

Glutamate-mediated excitotoxicity is known to cause secondary brain damage following stroke and traumatic brain injury (TBI). However, clinical trials using NMDA antagonists failed. Thus, glial excitatory amino acid transporters (EAATs) might be a promising target for therapeutic intervention. Methods and Results. We examined expression of EAAT1 (GLAST) and EAAT2 (Glt-1) in 36 TBI cases by immuno-histochemistry. Cortical expression of both EAATs decreased rapidly and widespread throughout the brain (in lesional, adjacent and remote areas) following TBI. In the white matter numbers of EAATI+ parenchymal cells increased 39-fold within 24h (p<0.001) and remained markedly elevated till later stages in the lesion (90-fold, p<0.01) and in perilesional regions (86-fold, p<0.01). In contrast, EAAT2+ parenchymal cells and EAATI+ or EAAT2+ perivascular cells did not increase significantly. Within the first days following TBI mainly activated microglia and thereafter mainly reactive astrocytes expressed EAAT1. Perivascular monocytes and foamy macrophages lacked EAATI immunoreactivity. We conclude that following TBI i) loss of cortical EAATs contributes to secondary brain damage, ii) glial EAAT 1 expression reflects a potential neuroprotective function of microglia and astrocytes, iii) microglial EAAT1 expression is restricted to an early stage of activation, iv) blood-derived monocytes do not express EAAT1 and v) pharmacological modification of glial EAAT expression might further limit neuronal damage.

Original languageEnglish
Pages (from-to)515-526
Number of pages12
JournalHistology and Histopathology
Volume22
Issue number4-6
Publication statusPublished - Apr 2007
Externally publishedYes

Keywords

  • Excitatory amino acid transporters
  • Microglial activation
  • Neuroprotection
  • Traumatic brain injury

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