ArticlePLoS biology2017
Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 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
- Sevoflurane, but not alphaxalone, causes lasting autism spectrum disorder-like pathology in male mice after exposure occurs during synaptogenesis.Neuropharmacology · 2026Article
- Effects of Sevoflurane on the Development of a Human Brain Microphysiological System.International journal of molecular sciences · 2026Article
- Neonatal sevoflurane anesthesia can also affect rat medulla spinalis.Asian biomedicine : research, reviews and news · 2025Article
- Rosiglitazone Promotes Oligodendrocyte Development and Myelin Formation of Repeated Neonatal Sevoflurane Exposure via PPARγ Signaling.Molecular neurobiology · 2025Article
- Anatomical site variations in healing of pediatric femoral shaft fractures: ultrasound evaluation of conservative treatment.Frontiers in pediatrics · 2025Article
- Zona incerta mediates early life isoflurane-induced fear memory deficits.Scientific reports · 2024Article
- Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway.International journal of molecular sciences · 2024Article
- Subunit-specific mechanisms of isoflurane-induced acute tonic inhibition in dentate gyrus granule neuron.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- 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
- Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain.Frontiers in aging neuroscience · 2023Article
- Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior.Frontiers in neurology · 2023Article
- Brief isoflurane administration as an adjunct treatment to control organophosphate-induced convulsions and neuropathology.Frontiers in pharmacology · 2023Article
- Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life.iScience · 2022Article
- Differential Effects of Sevoflurane Exposure on Long-Term Fear Memory in Neonatal and Adult Rats.Molecular neurobiology · 2022Article
- Hippocampal mTOR Dysregulation and Morphological Changes in Male Rats after Fetal Growth Restriction.Nutrients · 2022Article
- Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish.Molecular neurobiology · 2022Article
- Overexpression of miR-133b protects against isoflurane-induced learning and memory impairment.Experimental and therapeutic medicine · 2021Article
- Astrogliosis in juvenile non-human primates 2 years after infant anaesthesia exposure.British journal of anaesthesia · 2021Article
- Dendritic spine remodeling and plasticity under general anesthesia.Brain structure & function · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.
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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.