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Research Articles

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

November 2019

Maternal exposure to volatile anesthetics induces IL-6 in fetal brains and affects neuronal development.
European Journal of Pharmacology November 15, 2019

Traditional Chinese medicine, Kami-Shoyo-San protects ketamine-induced neurotoxicity in human embryonic stem cell-differentiated neurons through activation of brain-derived neurotrophic factor.
NeuroReport November 6, 2019

“Pediatric Anesthetic Neurotoxicity” Time to Stop!
Anesthesia & Analgesia November 5, 2019

Neurodevelopmental Effect of General Anesthesia on the Pediatric Patient.
Journal of Pediatric Ophthalmology and Strabismus November 1, 2019

Beyond Anesthesia Toxicity: Anesthetic Considerations to Lessen the Risk of Neonatal Neurological Injury
Anesthesia & Analgesia November 2019

Dexmedetomidine pretreatment attenuates isoflurane-induced neurotoxicity via inhibiting the TLR2/NF-κB signaling pathway in neonatal rats
Experimental and Molecular Pathology November 2019

Early Postnatal Exposure to Isoflurane Disrupts Oligodendrocyte Development and Myelin Formation in the Mouse Hippocampus
Perioperative Medicine November 2019

Sirtuin 2 Inhibition Attenuates Sevoflurane-Induced Learning and Memory Deficits in Developing Rats via Modulating Microglial Activation
Cellular and Molecular Neurobiology November 2019

Using animal models to evaluate the functional consequences of anesthesia during early neurodevelopment
Neurobiology of Learning and Memory November 2019

Voluntary Exercise Rescues the Spatial Memory Deficit Associated With Early Life Isoflurane Exposure in Male Rats
Anesthesia & Analgesia November 2019

October 2019

Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?
Pediatric Anesthesia October 31, 2019

Influence of general anesthetic exposure in developing brain on cognition and the underlying mechanisms
October 25, 2019

Sedation practices in pediatric patients with acute lymphoblastic leukemia.
Pediatric Blood & Cancer October 18, 2019

Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study.
Journal of Anesthesia October 14, 2019

General anesthetic neurotoxicity in the young: Mechanism and prevention.
Neuroscience & Biobehavioral Reviews October 10, 2019

Cognitive impairment and transcriptomic profile in hippocampus of young mice after multiple neonatal exposures to sevoflurane.
Aging October 3, 2019

Protective Effects of Xenon on Propofol-Induced Neurotoxicity in Human Neural Stem Cell-Derived Models.
Molecular Neurobiology October 2, 2019

The expression of glucose transporters and mitochondrial division and fusion proteins in rats exposed to hypoxic preconditioning to attenuate propofol neurotoxicity.
International Journal of Neuroscience October 2, 2019

Hypoxia, hypercarbia, and mortality reporting in studies of anaesthesia-related neonatal neurodevelopmental delay in rodent models: A systematic review.
European Journal of Anaesthesiology October 2019

LncRNA MALAT1 is involved in sevoflurane-induced neurotoxicity in developing rats.
Journal of Cellular Biochemistry October 2019

Maternal surgery during pregnancy has a transient adverse effect on the developing fetal rabbit brain
American Journal of Obstetrics and Gynecology October 2019

Mild hypothermia ameliorates anesthesia toxicity in the neonatal macaque brain
Neurobiology of Disease October 2019

The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis.
International Journal of Neuroscience October 2019

Xenon reduces sevoflurane-induced respiratory depression and neuro-apoptosis in immature rats
British Journal of Anaesthesia October 2019

FAQ

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.