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The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Glutamate excitotoxicity in a model of multiple sclerosis

Pitt, David, Werner, Peter, Raine, Cedric S.·2000·Nature Medicine
DOI 10.1038/71555
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Abstract

Glutamate excitotoxicity mediated by the AMPA/kainate type of glutamate receptors damages not only neurons but also the myelin-producing cell of the central nervous system, the oligodendrocyte. In multiple sclerosis, myelin, oligodendrocytes and some axons are lost as a result of an inflammatory attack on the central nervous system. Because glutamate is released in large quantities by activated immune cells, we expected that during inflammation in MS, glutamate excitotoxicity might contribute to the lesion. We addressed this by using the AMPA/kainate antagonist NBQX to treat mice sensitized for experimental autoimmune encephalomyelitis, a demyelinating model that mimics many of the clinical and pathologic features of multiple sclerosis. Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced dephosphorylation of neurofilament H, an indicator of axonal damage. Despite the clinical differences, treatment with NBQX had no effect on lesion size and did not reduce the degree of central nervous system inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect on the immune system. Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for multiple sclerosis.

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Crossref · 10.1038/71555

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1 of 1 references verified0 citation errors · 0 not checkable

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  • Neuroinflammation triggers the release of glutamate from neurons, infiltrating immune cells and microglia.

    “Given that neuroinflammation triggers the release of glutamate from neurons, infiltrating immune cells and microglia (21, 31), the rise in extracellular glutamate might present a central trigger for the induction of miR-92a also in inflamed neurons in vivo, especially since other inflammatory mediators including TNF-α, IFN-γ, or IL-1β failed to induce miR-92a expression.”

    From MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration (2023) · cites this paper as [21]

  • Modulation of glutamate receptor activity has been proven effective in ameliorating neuroaxonal damage in EAE.

    “Elevated glutamate has also been identified in brains of EAE mice, and modulation of glutamate receptor activity has been proven effective in ameliorating neuroaxonal damage in EAE (21, 34).”

    From MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration (2023) · cites this paper as [21]

  • Elevated glutamate has been identified in brains of EAE mice.

    “Elevated glutamate has also been identified in brains of EAE mice, and modulation of glutamate receptor activity has been proven effective in ameliorating neuroaxonal damage in EAE (21, 34).”

    From MicroRNA-92a–CPEB3 axis protects neurons against inflammatory neurodegeneration (2023) · cites this paper as [21]

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Research works printed but not linked: 20

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  16. Collins, R.C., Dobkin, B.H. & Choi, D.W. Selective vulnerability of the brain: new insights into the pathophysiology of stroke. Ann. Intern. Med. 110, 992–1000 (1989). · DOI
  17. O'Neill, M.J. et al. Decahydroisoquinolines: novel competitive AMPA/kainate antagonists with neuroprotective effects in global cerebral ischaemia. Neuropharmacology 37, 1211–1222 ( 1998). · DOI
  18. Rosenberg, L.J., Teng, Y.D., Wrathall, J. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline reduces glial loss and acute white matter pathology after experimental spinal cord contusion. J. Neurosci. 19, 464–475 (1999). · DOI
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Metadata

Authors
Pitt, D., Werner, P., & Raine, C. S.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2000-01
Volume
6
Issue
1
Pages
67-70
ISSN
  • 1078-8956
  • 1546-170X
DOI
10.1038/71555
Cited by
744
References
1
Language
en
Licence
www.springer.com/tdm (tdm)

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