title: Early expression of glutamate transporter proteins in ramified microglia after controlled cortical impact injury in the rat.
abstract: Traumatic brain injury is followed by increased extracellular glutamate concentration. Uptake of glutamate is mainly mediated by the glial glutamate transporters GLAST and GLT-1. Extent and distribution of GLAST and GLT-1 were studied in a rat model of controlled cortical impact injury (CCII). Western Blot analysis revealed lowest levels of GLAST and GLT-1 with a decrease by 40%-54% and 42%-49% between 24 and 72 h posttrauma. By 8 h after CCII, CSF glutamate levels were increased (10.5 microM vs. 2.56 microM in controls; P < 0.001), reaching maximum values by 48 h. A significant increase in de novo GLAST and GLT-1 expressing ramified microglia was observed within 4 h, reached a stable level by 48 h, and remained high up to 72 h after CCII. Furthermore, ramified microglia de novo expressed the neuronal glutamate transporter EAAC1 after CCII. Following CCII, GLAST/GLT-1 and GFAP coexpressing astrocytes were immediately reduced, reaching minimum levels within 8 h. This reduction of expression could be either due to protein downregulation or loss of astrocytes. At 72 h, a marked population of GLAST- and GLT-1-positive reactive astrocytes appeared. These results support the hypothesis that reduced astrocytic GLAST and GLT-1 protein levels following CCII contribute to evolving secondary injury. Microglia are capable of de novo expressing glutamate transporter proteins, indicating that the expression of glial and neuronal glutamate transporters is not restricted to a specific glial or neuronal lineage. Ramified microglia may play an important compensatory role in the early regulation of extracellular glutamate after CCII.
authors.affiliation: Institute of Neuropathology, Charité, Humboldt University, Berlin, Germany. frank.van_landeghem@charite.de
authors.forename: F K
authors.initials: FK
authors.lastname: van Landeghem
authors.forename: J F
authors.initials: JF
authors.lastname: Stover
authors.forename: I
authors.initials: I
authors.lastname: Bechmann
authors.forename: W
authors.initials: W
authors.lastname: Brück
authors.forename: A
authors.initials: A
authors.lastname: Unterberg
authors.forename: C
authors.initials: C
authors.lastname: Bührer
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D027342:Excitatory Amino Acid Transporter 2; D005110:Extracellular Space / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D037102:Lectins; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D027342:Excitatory Amino Acid Transporter 2; D005904:Glial Fibrillary Acidic Protein; D037102:Lectins; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid