title: Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain.
abstract: Excess activation of NMDA receptors is felt to participate in secondary neuronal damage after traumatic brain injury (TBI). Increased extracellular glutamate is active in this process and may result from either increased release or decreased reuptake. The two high-affinity sodium-dependent glial transporters [glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST)] mediate the bulk of glutamate transport. We studied the protein levels of GLT-1 and GLAST in the brains of rats after controlled cortical impact-induced TBI. With use of subtype-specific antibodies, GLT-1 and GLAST proteins were quantitated by immunoblotting in the ipsilateral and contralateral cortex at 2, 6, 24, 72, and 168 h after the injury. Sham-operated rats served as control. TBI resulted in a significant decrease in GLT-1 (by 20-45%; p < 0.05) and GLAST (by 30-50%; p < 0.05) protein levels between 6 and 72 h after the injury. D-[3H]Aspartate binding also decreased significantly (by 30-50%; p < 0.05) between 6 and 72 h after the injury. Decreased glial glutamate transporter function may contribute to the increased extracellular glutamate that may mediate the excitotoxic neuronal damage after TBI. This is a first report showing altered levels of glutamate transporter proteins after TBI.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin-Madison, and Veterans Affairs Hosptial, 53792, USA.
authors.forename: V L
authors.initials: VL
authors.lastname: Rao
authors.forename: M K
authors.initials: MK
authors.lastname: Başkaya
authors.forename: A
authors.initials: A
authors.lastname: Doğan
authors.forename: J D
authors.initials: JD
authors.lastname: Rothstein
authors.forename: R J
authors.initials: RJ
authors.lastname: Dempsey
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D001224:Aspartic Acid