TY - JOUR
T1 - Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury
AU - Beschorner, Rudi
AU - Dietz, K.
AU - Schauer, N.
AU - Mittelbronn, M.
AU - Schluesener, H. J.
AU - Trautmann, K.
AU - Meyermann, R.
AU - Simon, P.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Excitatory amino acid transporters
KW - Microglial activation
KW - Neuroprotection
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=34247544369&partnerID=8YFLogxK
M3 - Article
C2 - 17330806
AN - SCOPUS:34247544369
SN - 0213-3911
VL - 22
SP - 515
EP - 526
JO - Histology and Histopathology
JF - Histology and Histopathology
IS - 4-6
ER -