ArticleCurrent drug safety2012
Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway.
Article in Current drug safety, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 86 citations in OpenAlex.
- S-Ketamine Preserves Oxidative Metabolism and Reduces Metabolic Stress During Neuronal Hyperexcitability.International journal of molecular sciences · 2026Article
- α-tocopherol alleviates ketamine toxicity in rat brain neurons.BMC pharmacology & toxicology · 2026Article
- The ADNP-Mediated Transcriptome Response to Ketamine Impairs the Cytoskeletal Protein Axis.Journal of molecular neuroscience : MN · 2025Article
- Ketamine-Ethanol Combination Decreases Reduced Glutathione Levels and Activates both Intrinsic and Extrinsic Apoptotic Pathways Prior to Neuronal Death in SH-SY5Y Cells.Neurotoxicity research · 2025Article
- Protective effects of curcumin/magnesium oxide nanoparticles on ketamine-induced neurotoxicity in the mouse hippocampus.Research in pharmaceutical sciences · 2025Article
- The impact of ketamine and thiopental anesthesia on ultraweak photon emission and oxidative-nitrosative stress in rat brains.Frontiers in systems neuroscience · 2025Article
- Do Microplastics Have Neurological Implications in Relation to Schizophrenia Zebrafish Models? A Brain Immunohistochemistry, Neurotoxicity Assessment, and Oxidative Stress Analysis.International journal of molecular sciences · 2024Article
- Ketamine Clinical Use on the Pediatric Critically Ill Infant: A Global Bibliometric and Critical Review of Literature.Journal of clinical medicine · 2023Review
- The effects of general anesthetics on mitochondrial structure and function in the developing brain.Frontiers in neurology · 2023Review
- Combined Low Dose of Ketamine and Social Isolation: A Possible Model of Induced Chronic Schizophrenia-Like Symptoms in Male Albino Rats.Brain sciences · 2021Article
- Quantifying mitochondrial volume density in phrenic motor neurons.Journal of neuroscience methods · 2021Article
- A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly.Scientific reports · 2021Article
- Cortical Thickness Changes in Chronic Ketamine Users.Frontiers in psychiatry · 2021Article
- The Ketamine Antidepressant Story: New Insights.Molecules (Basel, Switzerland) · 2020Review
- Ketamine and Calcium Signaling-A Crosstalk for Neuronal Physiology and Pathology.International journal of molecular sciences · 2020Review
- Induced pluripotent stem cells as a platform to understand patient-specific responses to opioids and anaesthetics.British journal of pharmacology · 2020Review
- Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR.Molecular medicine reports · 2020Article
- Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy.Bioscience reports · 2020Article
- Article
- Ketamine-induced attenuation of reactive oxygen species in zebrafish is prevented by acetyl l-carnitine in vivo.Neuroscience letters · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may be possible to overcome these challenges by obtaining neurons from human embryonic stem cells (hESCs) in vitro. hESCs are able to replicate indefinitely and differentiate into every cell type. In this study, we investigated the toxic effect of ketamine on neurons differentiated from hESCs. Two-week-old neurons were treated with different doses and durations of ketamine with or without the reactive oxygen species (ROS) scavenger, Trolox. Cell viability, ultrastructure, mitochondrial membrane potential (ΔΨm), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose- and time-dependently caused cell death. In addition, ketamine decreased ΔΨm and increased cytochrome c release from mitochondria. Ketamine also increased ROS production and induced differential expression of oxidative stress-related genes. Specifically, abnormal ultrastructural and ΔΨm changes occurred earlier than cell death in the ketamine-induced toxicity process. Furthermore, Trolox significantly decreased ROS generation and attenuated cell death caused by ketamine in a dose-dependent manner. In conclusion, this study illustrates that ketamine time- and dose-dependently induces human neurotoxicity at supraclinical concentrations via ROS-mediated mitochondrial apoptosis pathway and that these side effects can be prevented by the antioxidant agent Trolox. Thus, hESC-derived neurons might provide a promising tool for studying anesthetic-induced developmental neurotoxicity and prevention strategies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.