Neurotoxicity caused by glutamate after subcritical hypoxia is prevented by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX): an in vitro study using rat hippocampal neurons.
Neurotoxicity of glutamate in conjunction with subcritical hypoxia was determined in vitro using hippocampal neurons obtained from 18-day-old rat fetuses. Neurons were plated at a low density and maintained for 3 days in a chemically defined medium without glutamate. When glutamate + was added after subcritical hypoxic stress, a low dose of glutamate, even at 10 microM, could cause significant neuronal loss in the following 24 h. The observed neurotoxicity to low glutamate dose (10-100 microM) could completely be prevented by 5 microM of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). This protective effect of CNQX was more potent than that of MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate). The mechanism by which glutamate is transformed from a neurotransmitter to a neurotoxin is discussed.
Kohmura
E
E
Department of Neurosurgery, Osaka University Medical School, Japan.
Yamada
K
K
Hayakawa
T
T
Kinoshita
A
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology*; D000860:Hypoxia / Q000150:complications*; D009422:Nervous System Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D011810:Quinoxalines; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter