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Research Articles

September 2020

Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1
Stem Cell Research & Therapy September 29, 2020

Anesthesia plus surgery in neonatal period impairs preference for social novelty in mice at the juvenile age.
Biochemical and Biophysical Research Communications September 24, 2020

Early childhood general anesthesia exposure associated with later developmental delay: A national population-based cohort study
PLOS One September 24, 2020

Protective role of protocatechuic acid in sevoflurane-induced neuron apoptosis, inflammation and oxidative stress in mice
Restorative Neurology and Neuroscience September 24, 2020

Conditions requiring hospitalisations, more than general anaesthesia itself, are associated with diagnosis of learning disorders in children
Anaesthesia Critical Care & Pain Medicine September 23, 2020

Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats
Brain and Behavior September 1, 2020

Is Anesthesia Bad for the Brain? Current Knowledge on the Impact of Anesthetics on the Developing Brain.
Anesthesiology Clinics September 2020

Sevoflurane Induces Hippocampal Neuronal Apoptosis by Altering the Level of Neuropeptide Y in Neonatal Rats.
Neurochemical Research September 2020

The protective effect of trilobatin against isoflurane-induced neurotoxicity in mouse hippocampal neuronal HT22 cells involves the Nrf2/ARE pathway
Toxicology September 2020

The Unspoken Question!
Anesthesia & Analgesia September 2020

May 2020

Optimization of Ultrasound Backscatter Spectroscopy to Assess Neurotoxic Effects of Anesthesia in the Newborn Non-human Primate Brain
Ultrasound in Medicine and Biology May 29, 2020

Neonatal Exposure to Anesthesia Leads to Cognitive Deficits in Old Age: Prevention With Intranasal Administration of Insulin in Mice
Neurotoxicity Research May 26, 2020

Neonatal Ketamine Alters High-Frequency Oscillations and Synaptic Plasticity in the Subiculum But Does not Affect Sleep Macrostructure in Adolescent Rats
Frontiers in Systems Neuroscience May 26, 2020

Neuroendocrine, epigenetic, and intergenerational effects of general anesthetics
World Journal of Psychiatry May 19, 2020

Upregulation of miR-215 attenuates propofol-induced apoptosis and oxidative stress in developing neurons by targeting LATS2.
Molecular Medicine May 6, 2020

Neurotoxicity of Sub-Anesthetic Doses of Sevoflurane and Dexmedetomidine Co-Administration in Neonatal Rats
NeuroToxicology May 5, 2020

Upregulation of miR-496 Rescues Propofol-Induced Neurotoxicity by Targeting Rho Associated Coiled-Coil Containing Protein Kinase 2 (ROCK2) in Prefrontal Cortical Neurons
Current Neurovascular Research May 5, 2020

Acetyl-l-carnitine Does Not Prevent Neurodegeneration in a Rodent Model of Prolonged Neonatal Anesthesia
Neurotoxicology and Teratology May 3, 2020

Standards for Preclinical Research and Publications in Developmental Anaesthetic Neurotoxicity: Expert Opinion Statement From the SmartTots Preclinical Working Group
British Journal of Anaesthesia May 2020

February 2020

False Interpretation of Scientific Data Leads to Biased Conclusions About the Association Between Cesarean Deliveries Under General Anesthesia and Risk of Autism Spectrum Disorder.
Journal of Autism and Developmental Disorders February 19, 2020

Resveratrol Mitigates Sevoflurane-Induced Neurotoxicity by the SIRT1-Dependent Regulation of BDNF Expression in Developing Mice
Oxidative Medicine and Cellular Longevity February 19, 2020

Neuroprotective effects of dexmedetomidine against the ketamine-induced disturbance of proliferation and differentiation of developing neural stem cells in the subventricular zone
BMC Neuroscience February 16, 2020

Cyclophilin D Contributes to Anesthesia Neurotoxicity in the Developing Brain
Frontiers in Cell and Developmental Biology February 11, 2020

MicroRNA-582-5p reduces propofol-induced apoptosis in developing neurons by targeting ROCK1.
Current Neurovascular Research February 7, 2020

Definition of Clinical Outcomes in Pediatric Anesthesia Research: It Is Like the Tower of Babel!
Anesthesia & Analgesia February 2020

Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice.
Neurochemical Research February 2020

Exogenous GM1 Ganglioside Attenuates Ketamine-Induced Neurocognitive Impairment in the Developing Rat Brain
Anesthesia & Analgesia February 2020

General anesthesia risk across pediatric surgical specialties: Low in otolaryngology
International Journal of Pediatric Otorhinolaryngology February 2020

January 2020

Dexmedetomidine Alleviates Neurogenesis Damage Following Neonatal Midazolam Exposure in Rats through JNK and P38 MAPK Pathways
ACS Chemical Neuroscience January 30, 2020

Effects of embryonic propofol exposure on axonal growth and locomotor activity in zebrafish
Journal of Applied Toxicology January 30, 2020

The mTOR Inhibitor Rapamycin Prevents General Anesthesia-Induced Changes in Synaptic Transmission and Mitochondrial Respiration in Late Postnatal Mice
Frontiers in Cellular Neuroscience January 28, 2020

Downregulation of CDK5 Restores Sevoflurane-Induced Cognitive Dysfunction by Promoting SIRT1-Mediated Autophagy.
Cellular and Molecular Neurobiology January 16, 2020

Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response
International Journal of Molecular Sciences January 10, 2020

General Anesthetic-Induced Neurotoxicity in the Immature Brain: Reevaluating the Confounding Factors in the Preclinical Studies.
Hindawi January 8, 2020

Exposure to Surgery and Anesthesia in Early Childhood and Subsequent Use of Attention Deficit Hyperactivity Disorder Medications.
Anesthesia & Analgesia January 8, 2020

Paediatric Anaesthesia Neurotoxicity: Bring Back the Papoose Board?
Oral Health January 7, 2020

Effects of Xenon-Based Anesthetic Exposure on the Expression Levels of Polysialic Acid Neural Cell Adhesion Molecule (PSA-NCAM) on Human Neural Stem Cell-Derived Neurons.
Molecular Neurobiology January 2020

General anesthesia in infants: neurobiological and neuropsychological concerns.
Boletin medico del Hospital Infantil de Mexico 2020

Ketamine exerts neurotoxic effects on the offspring of pregnant rats via the Wnt/β-catenin pathway.
Environmental Science and Pollution Research January 2020

NR2B receptor- and calpain-mediated KCC2 cleavage resulted in cognitive deficiency exposure to isoflurane
NeuroToxicology January 2020

Paeonol attenuates isoflurane anesthesia-induced hippocampal neurotoxicity via modulation of JNK/ERK/P38MAPK pathway and regulates histone acetylation in neonatal rat.
Journal of Maternal-Fetal and Neonatal Medicine January 2020

Vitexin improves neuron apoptosis and memory impairment induced by isoflurane via regulation of miR-409 expression.
Advances in Clinical and Experimental Medicine January 2020


What is SmartTots?
SmartTots is a Public-Private Partnership (PPP) between the US Food and Drug Administration (FDA) and the International Anesthesia Research Society (IARS). The mission of this partnership is to coordinate and fund a research program with the goal of ensuring safe surgery for the millions of infants and young children who undergo anesthesia and/or sedation each year.
What is the National Center for Toxicological Research (NCTR)?
NCTR is an internationally recognized research center at the FDA that supports the goal of improving patient and consumer safety. NCTR, along with other centers at the FDA, conducts research to support the scientific basis for the FDA’s regulatory decisions and reduce risks associated with products regulated by the FDA. One of the ways that NCTR helps assess possible risks to human health is to perform animal research studies that investigate the potential for adverse effects and mechanisms of injury following exposure to potentially dangerous chemicals.
How did the concerns about the safety of anesthetic drugs for infants and young children arise?
The FDA’s National Center for Toxicological Research (NCTR), as well as investigators at several universities, conducted research to study the effects of anesthetics on the nervous systems of developing animals. This research demonstrated that exposure to some anesthetics and sedatives caused memory and learning difficulties and other harmful changes in the central nervous systems of some laboratory animals. Currently, inadequate data exist to prove or disprove whether similar effects occur in children. More information on the results of early animal studies is below.
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Consensus Statement

A growing body of evidence from animal studies and observational studies in humans suggests adverse effects on behavior, learning, and memory may result from exposure to anesthetics and sedation during periods of rapid brain development. In June 2014 the International Anesthesia Research Society and US Food and Drug Administration convened a group of experts in anesthesia, pediatric medicine, neuroscience, and patient safety to consider the evidence and what it means for health care providers and parents.  The SmartTots Consensus Statement on the Use of Anesthetic and Sedative Drugs in Infants, Toddlers, and Preschool Children is the result of many hours of deliberation by that diverse group of experts along with feedback from more than 20 stakeholder organizations.

Scientific Presentations

IARS 2015 Annual Meeting and International Science Symposium

Improving Health through Discovery and Education

Neurotoxicity of Anesthetics in the Developing Brain – A Translational Update

Key Summary Points

Neurotoxicity of Anesthetics in the Developing Brain
  1. The major excitatory neurotransmitter, glutamate, and the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), are generally associated with neuronal communication in the adult brain.
  2. In the developing brain, these transmitters play a central role in brain morphogenesis, including synapse formation, proliferation, migration, differentiation and survival of neurons.