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

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108 Citations (Scopus)

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

Fingerprint

Dizocilpine Maleate
Neuroprotective Agents
N-Methyl-D-Aspartate Receptors
Oxygen
2-Amino-5-phosphonovalerate
Glucose
N-Methylaspartate
6-Cyano-7-nitroquinoxaline-2,3-dione
Neurons

Keywords

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

ASJC Scopus subject areas

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

Cite this

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title = "Antagonism of non-NMDA receptors augments the neuroprotective effect of NMDA receptor blockade in cortical cultures subjected to prolonged deprivation of oxygen and glucose",
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.",
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AU - Kaku, David A.

AU - Goldberg, Mark P.

AU - Choi, Dennis W.

PY - 1991/7/19

Y1 - 1991/7/19

N2 - 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.

AB - 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.

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