Early Exposure to Common Anesthetic Agents Causes Widespread Neurodegeneration in the Developing Rat Brain and Persistent Learning Deficits
Open accessAbstract
Recently it was demonstrated that exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors or drugs that potentiate GABA A receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blocking or GABA A receptor-enhancing properties. To induce or maintain a surgical plane of anesthesia, it is common practice in pediatric or obstetrical medicine to use agents from these two classes in combination. Therefore, the question arises whether this practice entails significant risk of inducing apoptotic neurodegeneration in the developing human brain. To begin to address this problem, we have administered to 7-d-old infant rats a combination of drugs commonly used in pediatric anesthesia (midazolam, nitrous oxide, and isoflurane) in doses sufficient to maintain a surgical plane of anesthesia for 6 hr, and have observed that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments.
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Exposure to NMDA antagonist, ethanol, or general anesthetics causes a significant increase in neuronal degeneration at P6-P7.
“For instance, exposure to N-methyl-D-aspartate (NMDA) antagonist, ethanol, or general anesthetics, causes a significant increase in neuronal degeneration at P6–P7456.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [6]
Interruption of neural activity during the critical period could cause deficits in brain functioning later in adulthood, including social deficits similar to ASD.
“Furthermore, these interruption could cause deficits in brain functioning later in adulthood6, including social deficits similar to those seen in autistic spectrum disorder (ASD)7.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [6]
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- Authors
- Jevtovic-Todorovic, V., Hartman, R. E., Izumi, Y., Benshoff, N. D., Dikranian, K., Zorumski, C. F., Olney, J. W., & Wozniak, D. F.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-02-01
- Volume
- 23
- Issue
- 3
- Pages
- 876-882
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6741934
- OpenAlex
- W2100569554
- Cited by
- 1,983
- References
- 30
- Citations by year
- 2026: 30 · 2025: 56 · 2024: 72 · 2023: 73 · 2022: 91 · 2021: 102 · 2020: 107 · 2019: 103 · 2018: 118 · 2017: 131 · 2016: 153 · 2015: 116 · 2014: 102 · 2013: 124 · 2012: 99
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HD37100, AG11355, 5k08da000406-06)
- National Institute on Alcohol Abuse and Alcoholism (AA 12951, R01AA012951)
- National Institute on Aging (AG11355, R01AG018434, P01AG011355, AG18434)
- National Institute of Mental Health (R01MH045493, MH45493)
- National Institute on Drug Abuse (R01DA005072, DA05072, Z01DA000406, K08 DA 00406)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD037100, R01HD037100, HD 37100)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- anesthetic neurotoxicity, NMDA receptor antagonists, GABA-A receptor agonists, midazolam, nitrous oxide, isoflurane, developing brain, learning deficits, memory impairment, pediatric anesthesia, obstetric anesthesia
- MeSH terms
- Anesthetics, Animals, Animals, Newborn, Behavior, Animal, Brain, Chronic Disease, Drug Combinations, Female, Hippocampus, Isoflurane, Learning Disabilities, Male, Memory Disorders, Midazolam, Synaptic Transmission, Nitrous Oxide, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Apoptosis, Long-Term Potentiation, Excitatory Amino Acid Antagonists, GABA Agonists, Maze Learning, Neurodegenerative Diseases, Rats, In Vitro Techniques
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