ArticleJournal of neurosurgical anesthesiology2019
Early Developmental Exposure to Repetitive Long Duration of Midazolam Sedation Causes Behavioral and Synaptic Alterations in a Rodent Model of Neurodevelopment.
Article in Journal of neurosurgical anesthesiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
The trial behind it
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Early Cognitive Function after Deep Sedation Using Different Anesthetic Agents in Pediatric Patients: A Prospective, Randomized Controlled Trial.Medicina (Kaunas, Lithuania) · 2024Trial
- Analgesia and sedation in premature infants receiving invasive ventilation: a systematic scoping review.Pediatric research · 2026Article
- Effects of Sevoflurane on the Development of a Human Brain Microphysiological System.International journal of molecular sciences · 2026Article
- Prolonged P14 latency predicts mortality in deep sedation: implications for neuroprotective sedation strategies.Intensive care medicine · 2025Article
- Comprehensive characterization of chronic midazolam exposure on neonates and long-term neurodevelopment.Molecular psychiatry · 2025Article
- Dexmedetomidine Versus Midazolam for Propofol Sparing in Procedural Sedation of Children With Leukemia: A Consecutive Case Series.Acta anaesthesiologica Scandinavica · 2025Observational
- ICU patient-on-a-chip emulating orchestration of mast cells and cerebral organoids in neuroinflammation.Communications biology · 2024Article
- Early Postnatal Exposure to Midazolam Causes Lasting Histological and Neurobehavioral Deficits via Activation of the mTOR Pathway.International journal of molecular sciences · 2024Article
- Medication Usage Record-Based Predictive Modeling of Neurodevelopmental Abnormality in Infants under One Year: A Prospective Birth Cohort Study.Healthcare (Basel, Switzerland) · 2024Article
- Experiencing anesthesia and surgery early in life impairs cognitive and behavioral development.Frontiers in neuroscience · 2024Article
- Review
- Article
- Decoding the Synaptic Proteome with Long-Term Exposure to Midazolam during Early Development.International journal of molecular sciences · 2022Article
- Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish.Molecular neurobiology · 2022Article
- Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Is Adult Hippocampal Neurogenesis Really Relevant for the Treatment of Psychiatric Disorders?Current neuropharmacology · 2021Review
- Effects of Midazolam on the Development of Adult Leydig Cells From Stem CellsFrontiers in endocrinology · 2021Article
- Cognitive Dysfunction After Analgesia and Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit.Frontiers in behavioral neuroscience · 2021Review
- Voltage dependent allosteric modulation of IPSCs by benzodiazepines.Brain research · 2020Article
- Potential Neurodevelopmental Effects of Pediatric Intensive Care Sedation and Analgesia: Repetitive Benzodiazepine and Opioid Exposure Alters Expression of Glial and Synaptic Proteins in Juvenile Rats.Critical care explorations · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
There is a large body of preclinical literature suggesting that exposure to general anesthetic agents during early life may have harmful effects on brain development. Patients in intensive care settings are often treated for prolonged periods with sedative medications, many of which have mechanisms of action that are similar to general anesthetics. Using in vivo studies of the mouse hippocampus and an in vitro rat cortical neuron model we asked whether there is evidence that repeated, long duration exposure to midazolam, a commonly used sedative in pediatric intensive care practice, has the potential to cause lasting harm to the developing brain. We found that mice that underwent midazolam sedation in early postnatal life exhibited deficits in the performance on Y-maze and fear-conditioning testing at young adult ages. Labeling with a nucleoside analog revealed a reduction in the rate of adult neurogenesis in the hippocampal dentate gyrus, a brain region that has been shown to be vulnerable to developmental anesthetic neurotoxicity. In addition, using immunohistochemistry for synaptic markers we found that the number of presynaptic terminals in the dentate gyrus was reduced, while the number of excitatory postsynaptic terminals was increased. These findings were replicated in a midazolam sedation exposure model in neurons in culture. We conclude that repeated, long duration exposure to midazolam during early development has the potential to result in persistent alterations in the structure and function of the brain.
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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.