Decreased expression of glutamate transporters in astrocytes after human traumatic brain injury.
The primary mechanism for eliminating synaptically released glutamate is uptake by astrocytes. In the present study, we examined whether traumatic brain injury (TBI) affects the cellular expression of glutamate transporters EAAT1 and EAAT2. Morphometrical immunohistochemical analysis demonstrated a predominant expression of EAAT1 and EAAT2 in astrocytes of normal human neocortex (n = 10). Following traumatic injury of human brain (n = 55), the number of EAAT2-positive cells was decreased for a prolonged survival period within the traumatized neocortex and the pericontusional region. GFAP-positive astrocytes decreased in number within the first 24 h. Thereafter, the number of GFAP-positive astrocytes increased again, indicating formation of reactive gliosis. Double immunofluorescence examinations revealed a reduction in absolute numbers of GFAP-positive astrocytes coexpressing EAAT1 or EAAT2 at survival times up to 7 days. In addition, the relative fractions of astrocytes coexpressing glutamate transporters decreased following TBI. We conclude that the posttraumatic reduction in cellular EAAT 1 and EAAT2 expression is predominantly due to degeneration of astrocytes and to downregulation in surviving astrocytes. Our results support the view that reduced glutamate uptake by astrocytes contributes to posttraumatic elevation of extracellular glutamate in humans.
van Landeghem
Frank K H
FK
Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany. frank.van_landeghem@charite.de
Weiss
Thorsten
T
Oehmichen
Manfred
M
von Deimling
Andreas
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein