HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

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

R. Beschorner1, K. Dietz2, N. Schauer1, M. Mittelbronn1, H.J. Schluesener1, K. Trautmann1, R. Meyermann1 and P. Simon1,3

1Institute of Brain Research, 2Department of Medical Biometry and 3Clinic of Internal Medicine, Department of Sports Medicine, Eberhard-Karls-University, Tuebingen, Germany

Offprint requests to: Rudi Beschorner, MD, Institute of Brain Research, University of Tuebingen, Calwestr. 3, 72076 Tuebingen, Germany. e-mail: rudi.beschorner@med.uni-tuebingen.de
R.B. and P.S. contributed equally to this study



Summary. 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 immunohistochemistry. 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 EAAT1+ 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 peri-lesional regions (86-fold, p<0.01). In contrast, EAAT2+ parenchymal cells and EAAT1+ 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 EAAT1 immunoreactivity. We conclude that following TBI i) loss of cortical EAATs contributes to secondary brain damage, ii) glial EAAT1 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. Histol Histopathol 22, 515-526 (2007)

Key words: Microglial activation, Neuroprotection, Traumatic brain injury, Excitatory amino acid transporters

DOI: 10.14670/HH-22.515