ArticleAnesthesia and analgesia2013
Ketamine enhances human neural stem cell proliferation and induces neuronal apoptosis via reactive oxygen species-mediated mitochondrial pathway.
Article in Anesthesia and analgesia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Mitochondrial dynamics and function in neural differentiation: a systematic review.European journal of medical research · 2025Pooled it
- Long term structural and functional neural changes following a single infusion of Ketamine in PTSD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- S-Ketamine Preserves Oxidative Metabolism and Reduces Metabolic Stress During Neuronal Hyperexcitability.International journal of molecular sciences · 2026Article
- Calcium Signaling Dysregulation as a Convergent Mechanism in Anesthetic-Induced Developmental Neurotoxicity.Drug design, development and therapy · 2026Review
- Comprehensive characterization of chronic midazolam exposure on neonates and long-term neurodevelopment.Molecular psychiatry · 2025Article
- Emergency care for children with sickle cell disease: a focus on pain and fever.Expert review of hematology · 2025Review
- Protective effects of curcumin/magnesium oxide nanoparticles on ketamine-induced neurotoxicity in the mouse hippocampus.Research in pharmaceutical sciences · 2025Article
- Neurotoxicity mechanisms and clinical implications of six common recreational drugs.Frontiers in pharmacology · 2025Review
- Assessing the developmental effects of fentanyl and impacts on lipidomic profiling using neural stem cell models.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Repeated Ketamine Anesthesia during the Neonatal Period Impairs Hippocampal Neurogenesis and Long-Term Neurocognitive Function by Inhibiting Mfn2-Mediated Mitochondrial Fusion in Neural Stem Cells.Molecular neurobiology · 2024Article
- Perioperative Ketamine and Cancer Recurrence: A Comprehensive Review.Journal of clinical medicine · 2024Review
- Psychopharmacological Approaches for Neural Plasticity and Neurogenesis in Major Depressive Disorders.Advances in experimental medicine and biology · 2024Review
- Ferrodifferentiation regulates neurodevelopment via ROS generation.Science China. Life sciences · 2023Article
- Mitochondrial Permeability Transition in Stem Cells, Development, and Disease.Advances in experimental medicine and biology · 2023Review
- The effects of general anesthetics on mitochondrial structure and function in the developing brain.Frontiers in neurology · 2023Review
- Ketamine induces rapid antidepressant effects via the autophagy-NLRP3 inflammasome pathway.Psychopharmacology · 2022Article
- Antidepressant Low Doses of Ketamine and Melatonin in Combination Produce Additive Neurogenesis in Human Olfactory Neuronal Precursors.Molecules (Basel, Switzerland) · 2022Article
- Bilirubin-Induced Neurological Damage: Current and Emerging iPSC-Derived Brain Organoid Models.Cells · 2022Review
- Article
- Norketamine, the Main Metabolite of Ketamine, Induces Mitochondria-Dependent and ER Stress-Triggered Apoptotic Death in Urothelial Cells via a CaInternational journal of molecular sciences · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGrowing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models, leading to a serious concern regarding the safety of pediatric anesthesia. However, if and how ketamine induces human neural cell toxicity is unknown. Recapitulation of neurogenesis from human embryonic stem cells (hESCs) in vitro allows investigation of the toxic effects of ketamine on neural stem cells (NSCs) and developing neurons, which is impossible to perform in humans. In the present study, we assessed the influence of ketamine on the hESC-derived NSCs and neurons.
methodshESCs were directly differentiated into neurons via NSCs. NSCs and 2-week-old neurons were treated with varying doses of ketamine for different durations. NSC proliferation capacity was analyzed by Ki67 immunofluorescence staining and bromodeoxyuridine assay. Neuroapoptosis was analyzed by TUNEL staining and caspase 3 activity measurement. The mitochondria-related neuronal apoptosis pathway including mitochondrial membrane potential, cytochrome c distribution within cells, mitochondrial fission, and reactive oxygen species (ROS) production were also investigated.
resultsKetamine (100 µM) increased NSC proliferation after 6-hour exposure. However, significant neuronal apoptosis was only observed after 24 hours of ketamine treatment. In addition, ketamine decreased mitochondrial membrane potential and increased cytochrome c release from mitochondria into cytosol. Ketamine also enhanced mitochondrial fission as well as ROS production compared with no-treatment control. Importantly, Trolox, a ROS scavenger, significantly attenuated the increase of ketamine-induced ROS production and neuronal apoptosis.
conclusionsThese data for the first time demonstrate that (1) ketamine increases NSC proliferation and causes neuronal apoptosis; (2) mitochondria are involved in ketamine-induced neuronal toxicity, which can be prevented by Trolox; and (3) the stem cell-associated neurogenesis system may provide a simple and promising in vitro model for rapidly screening anesthetic neurotoxicity and studying the underlying mechanisms as well as prevention strategies to avoid this toxic effect.
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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.