ArticleAnesthesiology2013
Anesthetics interfere with axon guidance in developing mouse neocortical neurons in vitro via a γ-aminobutyric acid type A receptor mechanism.
Article in Anesthesiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 70 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
- Pain and anesthesia - on fetal nervous system and brain development.Frontiers in pharmacology · 2025Review
- 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
- Sevoflurane exposure during the second trimester induces neurotoxicity in offspring rats by hyperactivation of PARP-1.Psychopharmacology · 2022Article
- Blockade of the NLRP3/caspase-1 axis attenuates ketamine-induced hippocampus pyroptosis and cognitive impairment in neonatal rats.Journal of neuroinflammation · 2021Article
- Gonadal hormone-independent sex differences in GABABritish journal of pharmacology · 2020Article
- Sevoflurane Exposure Induces Neuronal Cell Parthanatos Initiated by DNA Damage in the Developing Brain via an Increase of Intracellular Reactive Oxygen Species.Frontiers in cellular neuroscience · 2020Article
- The Effects of General Anesthetics on Synaptic Transmission.Current neuropharmacology · 2020Review
- Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment.Neurobiology of learning and memory · 2019Review
- General anesthetic exposure in adolescent rats causes persistent maladaptations in cognitive and affective behaviors and neuroplasticity.Neuropharmacology · 2019Article
- Repeated neonatal isoflurane exposures in the mouse induce apoptotic degenerative changes in the brain and relatively mild long-term behavioral deficits.Scientific reports · 2019Article
- Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice.Psychopharmacology · 2019Article
- Electroacupuncture decreases Netrin-1-induced myelinated afferent fiber sprouting and neuropathic pain through μ-opioid receptors.Journal of pain research · 2019Article
- Pilose antler polypeptide protects against sevoflurane‑mediated neurocyte injury.Molecular medicine reports · 2018Article
- Early Developmental Exposure to General Anesthetic Agents in Primary Neuron Culture Disrupts Synapse Formation via Actions on the mTOR Pathway.International journal of molecular sciences · 2018Article
- Neonatal anesthesia exposure impacts brain microRNAs and their associated neurodevelopmental processes.Scientific reports · 2018Article
- General Anesthesia and Young Brain: What is New?Journal of neurosurgical anesthesiology · 2018Review
- Exposure of Developing Brain to General Anesthesia: What Is the Animal Evidence?Anesthesiology · 2018Review
- Early Exposure to Ketamine Impairs Axonal Pruning in Developing Mouse Hippocampus.Molecular neurobiology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe finding that exposure to general anesthetics (GAs) in childhood may increase rates of learning disabilities has raised a concern that anesthetics may interfere with brain development. The generation of neuronal circuits, a complex process in which axons follow guidance cues to dendritic targets, is an unexplored potential target for this type of toxicity.
methodsGA exposures were conducted in developing neocortical neurons in culture and in early postnatal neocortical slices overlaid with fluorescently labeled neurons. Axon targeting, growth cone collapse, and axon branching were measured using quantitative fluorescence microscopy.
resultsIsoflurane exposure causes errors in Semaphorin-3A-dependent axon targeting (n = 77 axons) and a disruption of the response of axonal growth cones to Semaphorin-3A (n = 2,358 growth cones). This effect occurs at clinically relevant anesthetic doses of numerous GAs with allosteric activity at γ-aminobutyric acid type A receptors, and it was reproduced with a selective agonist. Isoflurane also inhibits growth cone collapse induced by Netrin-1, but does not interfere branch induction by Netrin-1. Insensitivity to guidance cues caused by isoflurane is seen acutely in growth cones in dissociated culture, and errors in axon targeting in brain slice culture occur at the earliest point at which correct targeting is observed in controls.
conclusionsThese results demonstrate a generalized inhibitory effect of GAs on repulsive growth cone guidance in the developing neocortex that may occur via a γ-aminobutyric acid type A receptor mechanism. The finding that GAs interfere with axon guidance, and thus potentially with circuit formation, represents a novel form of anesthesia neurotoxicity in brain development.
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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.