Antagonism of non-NMDA receptors augments the neuroprotective effect of NMDA receptor blockade in cortical cultures subjected to prolonged deprivation of oxygen and glucose

David A. Kaku, Mark P. Goldberg, Dennis W. Choi

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

A 30-60 min period of oxygen and glucose deprivation induced widespread degeneration of cultured murine neocortical neurons. Neuronal degeneration could be blocked by adding the selective NMDA antagonist MK-801 to the bathing medium; however, if the deprivation period was prolonged to 90-105 min, the neuroprotective effect of MK-801 was overcome. The non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) at 1-100 μM concentrations also failed to protect neurons against this prolonged insult, but te combination of CNQX with either MK-801 or d-APV produced marked neuroprotection. This synergistic actuon of CNQX was not due to enhanced blockage of NMDA receptors, as it was not mimicked by combining MK-801 with d-APV or 7-chlorokynurenate. These observations support the idea that combined NMDA and non-NMDA receptor blockade may have value in ameliorating the neuronal loss associated with prolonged ischemic insults in vivo.

Original languageEnglish (US)
Pages (from-to)344-347
Number of pages4
JournalBrain Research
Volume554
Issue number1-2
DOIs
StatePublished - Jul 19 1991

Keywords

  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Cell culture
  • Glutamate
  • Hypoxia
  • Ischemia
  • MK-801
  • Neurotoxicity
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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