QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, S. Articles by Stys, P. K. Search for Related Content PubMed PubMed Citation Articles by Li, S. Articles by Stys, P. K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUTAMIC ACID HYDROCHLORIDE SODIUM Medline Plus Health Information Spinal Cord Injuries

 Previous Article  |  Next Article 

The Journal of Neuroscience, 1999, 19:RC16:1-9

RAPID COMMUNICATION
Novel Injury Mechanism in Anoxia and Trauma of Spinal Cord White Matter: Glutamate Release via Reverse Na⁺-dependent Glutamate Transport

Shuxin Li¹, Geoff A. R. Mealing², Paul Morley², and Peter K. Stys¹

¹ Loeb Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada, K1Y 4K9, and ² Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6

Spinal cord injury is a devastating condition, with much of the clinical disability resulting from disruption of white matter tracts. Recent reports suggest a component of glutamate excitotoxicity in spinal cord injury. In this study, the role of glutamate and mechanism of release of this excitotoxin were investigated in rat dorsal column slices subjected to 60 min of anoxia or 15 sec of mechanical compression at a force of 2 gm in vitro. The broad-spectrum glutamate antagonist kynurenic acid (1 mM) and the selective AMPA antagonist GYKI52466 (30 µM) were protective against anoxia (compound action potential amplitude recovered to 56 vs 27% without drug). GYKI52466 was also effective against trauma (65 vs 35%). Inhibition of Na⁺-dependent glutamate transport with dihydrokainate or L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM each) protected against anoxia (65-75 vs 25%) and trauma (70 vs 35%). The depletion of cytosolic glutamate in axon cylinders and oligodendrocytes by anoxia was completely prevented by glutamate transport inhibition. Immunohistochemistry revealed that a large component of injury occurred in the myelin sheath and was prevented by AMPA receptor blockade or glutamate transport inhibitors. We conclude that release of glutamate by reversal of Na⁺-dependent glutamate transport with subsequent activation of AMPA receptors is an important mechanism in spinal cord white matter anoxic and traumatic injury.

Key words: spinal cord injury; axon; anoxia; trauma; AMPA; Na⁺-glutamate transport; myelin; dihydrokainate; L-trans-pyrrolidine-2,4-dicarboxylic acid; GYKI52466; kynurenic acid

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/$05.00/0

This article has been cited by other articles:

				K. Kolodziejczyk, N. B. Hamilton, A. Wade, R. Karadottir, and D. Attwell The effect of N-acetyl-aspartyl-glutamate and N-acetyl-aspartate on white matter oligodendrocytes Brain, June 1, 2009; 132(6): 1496 - 1508. [Abstract] [Full Text] [PDF]

				M. A. Nikolaeva, S. Richard, A. Mouihate, and P. K. Stys Effects of the Noradrenergic System in Rat White Matter Exposed to Oxygen-Glucose Deprivation In Vitro J. Neurosci., February 11, 2009; 29(6): 1796 - 1804. [Abstract] [Full Text] [PDF]

				M. Domercq, M. V. Sanchez-Gomez, C. Sherwin, E. Etxebarria, R. Fern, and C. Matute System xc- and Glutamate Transporter Inhibition Mediates Microglial Toxicity to Oligodendrocytes J. Immunol., May 15, 2007; 178(10): 6549 - 6556. [Abstract] [Full Text] [PDF]

				W. J. McCarran and M. P. Goldberg White Matter Axon Vulnerability to AMPA/Kainate Receptor-Mediated Ischemic Injury Is Developmentally Regulated J. Neurosci., April 11, 2007; 27(15): 4220 - 4229. [Abstract] [Full Text] [PDF]

				M. Ouardouz, S. Malek, E. Coderre, and P. K. Stys Complex interplay between glutamate receptors and intracellular Ca2+ stores during ischaemia in rat spinal cord white matter J. Physiol., November 15, 2006; 577(1): 191 - 204. [Abstract] [Full Text] [PDF]

				P. K. Stys and S. Li Glutamate-Induced White Matter Injury: Excitotoxicity without Synapses Neuroscientist, August 1, 2000; 6(4): 230 - 233. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help