title: Concentrations of glutamate released following spinal cord injury kill oligodendrocytes in the spinal cord.
abstract: We investigated in vivo in rats whether sufficient glutamate is released following spinal cord injury (SCI) to kill oligodendrocytes. Microdialysis sampling was used to establish the level of glutamate released (550 +/- 80 microM) in the white matter during SCI. This glutamate concentration was administered into the spinal cords of other rats and the densities of oligodendrocytes remaining 24 and 72 h later determined by counting cells immunostained with the oligodendrocyte marker CC-1. Administration of ACSF, 4.0 mM glutamate (estimated resulting tissue exposure 500 microM) and 10.0 mM glutamate by microdialysis reduced oligodendrocyte density 22%, 57%, and 74%, respectively, relative to normal at 24 h post-exposure. Therefore, sufficient glutamate is released following SCI to damage white matter. Oligodendrocyte densities near the fiber track were not significantly different at 72 h from 24 h post-exposure, so most glutamate-induced oligodendrocyte death occurs within 24 h after exposure. Injecting the AMPA/kainate receptor blocker NBQX into the spinal cord during glutamate administration reduced the glutamate-induced decrease in oligodendrocyte density, evidence for AMPA/kainate receptor involvement in glutamate-induced oligodendrocyte death. This work directly demonstrates in vivo that following SCI glutamate reaches concentrations toxic to white matter and that AMPA/kainate receptors mediate this glutamate toxicity to oligodendrocytes.
authors.affiliation: Department of Neurosciences and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1043, USA.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Xu
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hughes
authors.forename: Zaiming
authors.initials: Z
authors.lastname: Ye
authors.forename: Claire E
authors.initials: CE
authors.lastname: Hulsebosch
authors.forename: David J
authors.initials: DJ
authors.lastname: McAdoo
mesh_terms: D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid