Skip Navigation LinksHome > June 2014 - Volume 73 - Issue 6 > N-Methyl-D-Aspartate Receptor Blockade Is Neuroprotective in...
Journal of Neuropathology & Experimental Neurology:
doi: 10.1097/NEN.0000000000000073
Original Articles

N-Methyl-D-Aspartate Receptor Blockade Is Neuroprotective in Experimental Autoimmune Optic Neuritis

Sühs, Kurt-Wolfram MD; Fairless, Richard PhD; Williams, Sarah K. PhD; Heine, Katrin; Cavalié, Adolfo PhD; Diem, Ricarda MD

Supplemental Author Material
Collapse Box

Abstract

Optic neuritis is a common clinical manifestation of the chronic inflammatory CNS disease multiple sclerosis that can result in persistent visual impairment caused by degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs). Using a model of experimental autoimmune encephalomyelitis with optic neuritis (Brown Norway rats), we show that administration of the N-methyl-D-aspartate (NMDA) receptor antagonists memantine or MK801 results in RGC protection, axon protection, and reduced demyelination of optic nerves. Calcium imaging revealed that RGC responses to glutamate stimulation predominantly occurred via NMDA receptors and were inhibited by memantine in a dose-dependent manner. In contrast, oligodendrocytes were mainly responsive through the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor. This suggests that NMDA receptor blockade protected RGCs directly and that the protection was independent of effects on oligodendrocytes. Moreover, increased RGC survival was observed before the onset of optic nerve demyelination—when RGC degeneration had already started. These results indicate an important pathophysiologic role for NMDA receptor–mediated glutamate toxicity during the induction phase of this disease model and highlight a potential target for therapeutic neuroprotection in human optic neuritis.

Copyright © 2014 by the American Association of Neuropathologists, Inc.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.