Blockade of glutamate receptors unmasks neuronal apoptosis after oxygen-glucose deprivation in vitro.
Mouse cortical cell cultures exposed to transient oxygen-glucose deprivation developed marked acute cell body swelling followed by neurodegeneration, consistent with necrosis-type death. This death was not attenuated by the protein synthesis inhibitor, cycloheximide, but was attenuated by addition of the N-methyl-D-asparate antagonist, MK-801 (dizocilpine maleate), and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. If the deprivation insult was extended to overcome the protective effect of glutamate antagonists, neuronal death resulted that was associated with cell body shrinkage and DNA fragmentation, and was attenuated by cycloheximide. These data suggest that oxygen-glucose deprivation can induce in cortical neurons both excitotoxic necrosis, and apoptosis dependent on new macromolecule synthesis.
Gwag
B J
BJ
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Lobner
D
D
Koh
J Y
JY
Wie
M B
MB
Choi
D W
DW
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000633:toxicity; D005947:Glucose / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D003470:Culture Media; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D011500:Protein Synthesis Inhibitors; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003513:Cycloheximide; D005947:Glucose