title: Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury.
abstract: Increases in brain interstitial excitatory amino acid (EAA(I)) concentrations after ischemia are ameliorated by use-dependent Na+ channel antagonists and by supplementing interstitial glucose, but the regulation of EAA(I) after traumatic brain injury (TBI) is unknown. We studied the regulation of EAA(I) after TBI using the controlled cortical impact model in rats. To monitor changes in EAA(I), microdialysis probes were placed in the cortex adjacent to the contusion and in the ipsilateral hippocampus. Significant increases in dialysate EAA(I) after TBI were found compared to levels measured in sham controls. Treatment with the use-dependent Na+ channel antagonist 619C89 (30 mg/kg i.v.) did not significantly decrease dialysate glutamate compared to vehicle controls in hippocampus (10.4+/-2.4 vs. 11.9+/-1.6 microM), but there was significant decrease in dialysate glutamate in cortex after 619C89 treatment (19.3+/-3 vs. 12.6+/-1.1 microM, P<0.05). Addition of 30 mM glucose to the dialysate, a treatment that decreases EAA(I) after ischemia, had no significant effect upon dialysate glutamate after TBI in cortex (20.0+/-4.9 vs. 11.7+/-3.4 microM) or in hippocampus (10.9+/-2.0 vs. 8.9+/-2.4 microM). These results suggest that neither increased release of EAAs due to Na+ channel-mediated depolarization nor failure of glutamate reuptake due to glucose deprivation can explain the majority of the increase in EAA(I) following TBI.
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Rose
authors.forename: Michele B
authors.initials: MB
authors.lastname: Huerbin
authors.forename: John
authors.initials: J
authors.lastname: Melick
authors.forename: Donald W
authors.initials: DW
authors.lastname: Marion
authors.forename: Alan M
authors.initials: AM
authors.lastname: Palmer
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Schiding
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Steven H
authors.initials: SH
authors.lastname: Graham
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000096:biosynthesis / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018846:Excitatory Amino Acids