ArticleInternational journal of molecular sciences2018
Early Developmental Exposure to General Anesthetic Agents in Primary Neuron Culture Disrupts Synapse Formation via Actions on the mTOR Pathway.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Effects of Anesthesia Neurotoxicity on Oligodendrocyte Development and Myelination: An In Vitro Study Using Primary Cultures.International journal of molecular sciences · 2026Article
- Effects of Sevoflurane on the Development of a Human Brain Microphysiological System.International journal of molecular sciences · 2026Article
- From neurotoxicity to neuroprotection: Rethinking GABACell biology and toxicology · 2025Review
- Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway.International journal of molecular sciences · 2024Article
- General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain.Zoological research · 2024Review
- Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway.International journal of molecular sciences · 2023Article
- Neonatal sevoflurane exposure induces long-term changes in dendritic morphology in juvenile rats and mice.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain.Frontiers in aging neuroscience · 2023Article
- Article
- lncRNA BDNF-AS Attenuates Propofol-Induced Apoptosis in HT22 Cells by Modulating the BDNF/TrkB Pathway.Molecular neurobiology · 2022Article
- Hippocampal mTOR Dysregulation and Morphological Changes in Male Rats after Fetal Growth Restriction.Nutrients · 2022Article
- MicroRNA-8126-Mediated Antioxidant Stress Attenuates Isoflurane-Induced Hippocampal Neurotoxicity in Developing Rats.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Research progress on molecular mechanisms of general anesthetic-induced neurotoxicity and cognitive impairment in the developing brain.Frontiers in neurology · 2022Review
- Tetraethylammonium chloride reduces anaesthetic-induced neurotoxicity in Caenorhabditis elegans and mice.British journal of anaesthesia · 2022Article
- Repeated neonatal sevoflurane induced neurocognitive impairment through NF-κB-mediated pyroptosis.Journal of neuroinflammation · 2021Article
- Early Isoflurane Exposure Impairs Synaptic Development in Fmr1 KO Mice via the mTOR Pathway.Neurochemical research · 2021Article
- A synthetic peptide rescues rat cortical neurons from anesthetic-induced cell death, perturbation of growth and synaptic assembly.Scientific reports · 2021Article
- Isoflurane Exposure in Juvenile Caenorhabditis elegans Causes Persistent Changes in Neuron Dynamics.Anesthesiology · 2020Article
- Linoleic acid-derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron-glia co-cultures in a sex-dependent manner.Journal of neurochemistry · 2020Article
- Resveratrol Mitigates Sevoflurane-Induced Neurotoxicity by the SIRT1-Dependent Regulation of BDNF Expression in Developing Mice.Oxidative medicine and cellular longevity · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Human epidemiologic studies and laboratory investigations in animal models suggest that exposure to general anesthetic agents (GAs) have harmful effects on brain development. The mechanism underlying this putative iatrogenic condition is not clear and there are currently no accepted strategies for prophylaxis or treatment. Recent evidence suggests that anesthetics might cause persistent deficits in synaptogenesis by disrupting key events in neurodevelopment. Using an in vitro model consisting of dissociated primary cultured mouse neurons, we demonstrate abnormal pre- and post-synaptic marker expression after a clinically-relevant isoflurane anesthesia exposure is conducted during neuron development. We find that pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) pathway can reverse the observed changes. Isoflurane exposure increases expression of phospho-S6, a marker of mTOR pathway activity, in a concentration-dependent fashion and this effect occurs throughout neuronal development. The mTOR 1 complex (mTORC1) and the mTOR 2 complex (mTORC2) branches of the pathway are both activated by isoflurane exposure and this is reversible with branch-specific inhibitors. Upregulation of mTOR is also seen with sevoflurane and propofol exposure, suggesting that this mechanism of developmental anesthetic neurotoxicity may occur with all the commonly used GAs in pediatric practice. We conclude that GAs disrupt the development of neurons during development by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.
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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.