The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain
Abstract
Ketamine, a widely used pediatric anesthetic, has been associated with enhanced neuronal toxicity in the developing brain, but mechanisms and neuronal susceptibility to neurotoxic insult leading to neuronal cell death remain poorly defined. One of the main goals of this study was to determine whether there is a duration of ketamine‐induced anesthesia below which no significant ketamine‐induced neurodegeneration can be detected. Newborn rhesus monkeys (postnatal day 5 or 6) were administered ketamine intravenously for 3, 9 or 24 h to maintain a steady anesthetic plane, followed by a 6‐h withdrawal period. The 9‐ and 24‐h durations were selected as relatively long and extremely long exposures, respectively, while the 3‐h treatment more closely approximates a typical duration of pediatric general anesthesia. Animals were subsequently perfused under anesthesia and brain tissue was processed for analyses using silver and Fluoro‐Jade C stains and caspase‐3 immunostain. The results indicated that no significant neurotoxic effects occurred if the anesthesia duration was 3 h. However, ketamine infusions for either 9 or 24 h significantly increased neuronal cell death in layers II and III of the frontal cortex. Although a few caspase‐3‐ and Fluoro‐Jade C‐positive neuronal profiles were observed in some additional brain areas including the hippocampus, thalamus, striatum and amygdala, no significant differences were detected between ketamine‐treated and control monkeys in these areas after 3, 9 or 24 h of exposure. These data show that treatment with ketamine up to 3 h is without adverse effects as determined by nerve cell death. However, anesthetic durations of 9 h or greater are associated with significant brain cell death in the frontal cortex. Thus, the threshold duration below which no neurotoxicity would be expected is somewhere between 3 and 9 h.
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Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
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Effects of Ketamine in Normal and Schizophrenic Volunteers
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Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons
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Ketamine-Induced Neuronal Cell Death in the Perinatal Rhesus Monkey
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Self-citationKetamine: Teaching an Old Drug New Tricks
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Brambrink, A. M., Back, S. A., Riddle, A., Gong, X., Moravec, M. D., Dissen, G. A., Creeley, C. E., Dikranian, K. T., & Olney, J. W. (2012) · Annals of Neurology · doi:10.1002/ana.23652 · Cited by 264
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148
Acevedo-Diaz, E. E., Cavanaugh, G. W., Greenstein, D., Kraus, C., Kadriu, B., Zarate, C. A., & Park, L. T. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.11.028 · Cited by 113
Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain
Creeley, C. E., Dikranian, K. T., Johnson, S. A., Farber, N. B., & Olney, J. W. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-23 · Cited by 84
Metadata
- Authors
- Zou, X., Patterson, T. A., Divine, R. L., Sadovova, N., Zhang, X., Hanig, J. P., Paule, M. G., Slikker, W., & Wang, C.
- Venue
- International Journal of Developmental Neuroscience
- Publisher
- Wiley
- Published
- 2009-07-04
- Volume
- 27
- Issue
- 7
- Pages
- 727-731
- ISSN
- 0736-5748 (ISSN-L)
- 1873-474X
- OpenAlex
- W1999711595
- Cited by
- 260
- References
- 27
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
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- Zou, X., Patterson, T. A., Divine, R. L., Sadovova, N., Zhang, X., Hanig, J. P., Paule, M. G., Slikker, W., & Wang, C. (2009). Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. International Journal of Developmental Neuroscience. https://doi.org/10.1016/j.ijdevneu.2009.06.010
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