Blockade of N-Methyl-D-Aspartate Receptors by Ketamine Produces Loss of Postnatal Day 3 Monkey Frontal Cortical Neurons in Culture

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic. Recent data suggest that anesthetic drugs may cause neurodegeneration during development. The purpose of this study was to determine the robustness of ketamine-induced developmental neurotoxicity...

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Bibliographic Details
Published in:Toxicological sciences 2006-05, Vol.91 (1), p.192-201
Main Authors: Wang, Cheng, Sadovova, Natalya, Hotchkiss, Charlotte, Fu, Xin, Scallet, Andrew C., Patterson, Tucker A., Hanig, Joseph, Paule, Merle G., Slikker, William
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
antisense oligonucleotide
Base Sequence
Cell Death - drug effects
DNA Primers
Excitatory Amino Acid Antagonists - pharmacology
Female
Frontal Lobe - cytology
Frontal Lobe - drug effects
Frontal Lobe - growth & development
Frontal Lobe - metabolism
Immunohistochemistry
In Situ Nick-End Labeling
in vitro
ketamine
Ketamine - pharmacology
Macaca mulatta
Male
neonatal rhesus monkey
neurodegeneration
Neurons - drug effects
Neurons - metabolism
NF-kappa B - metabolism
NMDA receptor
Protein Transport
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
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Summary:Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic. Recent data suggest that anesthetic drugs may cause neurodegeneration during development. The purpose of this study was to determine the robustness of ketamine-induced developmental neurotoxicity using rhesus monkey frontal cortical cultures and also to determine if dysregulation of NMDA receptor subunits promotes ketamine-induced cell death. Frontal cortical cells collected from the neonatal monkey were incubated for 24 h with 1, 10, or 20μM ketamine alone or with ketamine plus either NR1 antisense oligonucleotides or the nuclear factor kB translocation inhibitor, SN-50. Ketamine caused a marked reduction in the neuronal marker polysialic acid neural cell adhesion molecule and mitochondrial metabolism, as well as an increase in DNA fragmentation and release of lactate dehydrogenase. Ketamine-induced effects were blocked by NR1 antisenses and SN-50. These data suggest that NR1 antisenses and SN-50 offer neuroprotection from the enhanced degeneration induced by ketamine in vitro.
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfj144