Research Articles

Neurotoxicity, general anesthesia in young children, and a survey of current pediatric anesthesia practice at US teaching institutions
Pediatric Anesthesia, Ward CG, Hines SJ, Maxwell LG, McGowan FX, Sun LS.

October

Neuroinflammation and Ischemic Neurodegeneration in the Central Nervous System of Newborn Piglets After Isoflurane Anesthesia

Presented at ASA, October 27, 2015

Dexmedetomidine Mitigates Neuroapoptosis Induced by Prenatal Intravenous Anesthetic Exposure in Rats
Presented at ASA, October 26, 2015

Latent Class Analysis of Neuropsychological Deficit After Exposure to Anesthesia in Early Childhood
Presented as ASA, October 26, 2015

Identifying Children at Risk for Anesthetic Neurotoxicity
Presented as ASA,October 24, 2015

Development of a Translational, Preclinical Piglet Model of Anesthesia-Induced Neurotoxicity Mechanisms in the Pediatric Population
Presented at ASA, October 24, 2015

Estimation and Analysis of Unnecessarily Early Procedures in Infants Younger than Six Month of Age in the United States
Presented at ASA, October 24, 2015

Neonatal MRI: Can We Reduce Anesthesia Exposure? A National Survey
Presented at ASA, October 24, 2015

Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study
The Lancet, October 2015

September

Neonatal anesthesia: how we manage our most vulnerable patients
Korean J Anesthesiol. 2015 Oct; 68(5): 434–441.
Published online 2015 Sep 30.

August

Efficacy of rutin in inhibiting neuronal apoptosis and cognitive disturbances in sevoflurane or propofol exposed neonatal mice
Int J Clin Exp Med. 2015; 8(8): 14397–14409.
Published online 2015 Aug 15.

Pediatric dental sedation: challenges and opportunities
Clin Cosmet Investig Dent. 2015; 7: 97–106.
Published online 2015 Aug 26.

July

Long-Term Behavioral Effects in a Rat Model of Prolonged Postnatal Morphine Exposure
Behavioral Neuroscience, Vol 129(5),
Craig, M. M., & Bajic, D. (2015, July 27).

Long-term action of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rats
Int J Clin Exp Med. 2015; 8(7): 10696–10704.
Published online 2015 Jul 15.

Neuroprotective properties of vitamin C on equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in high fat diet fed neonatal mice
Int J Clin Exp Med. 2015; 8(7): 10444–10458.
Published online 2015 Jul 15.

Anesthetic use in newborn infants: the urgent need for rigorous evaluation
Pediatr Res. 2015 Jul; 78(1): 2–6.
Published online 2015 Apr 8.

Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia
Pediatrics, June 2015
Barynia Backeljauw, Scott K. Holland, Mekibib Altaye, Andreas W. Loepke

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation
CNS Drugs, July 2015, Volume 29, Issue 7, pp 543-563

Age-dependent electroencephalogram (EEG) patterns during sevoflurane general anesthesia in infants
eLIFE, July 2015

Age-dependency of sevoflurane-induced electroencephalogram dynamics in children
British Journal of Anaesthesia, 2015

June

Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia
Pediatrics, June 2015.
Backeljawu B, Holland SK, Altaye M, Loepke AW

microRNA Expression Profiling of Propofol-Treated Developing Rat Hippocampal
DNA Cell Biol, June 2015.
Sun W, Pei L

Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy
Cochrane Database Syst Rev., June 2015.
Jones LJ, Craven PD, Lakkundi A, Foster JP, Badawi N

Ketamine-Induced Toxicity in Neurons Differentiated from Neural Stem Cells
Mol Neurobiol, June 2015.
Slikker W Jr, Liu F, Rainosek SW, Patterson TA, Sadovova N, Hanig JP, Paule MG, Wang C

Early Exposure to General Anesthesia Disrupts Spatial Organization of Presynaptic Vesicles in Nerve Terminals of the Developing Rat Subiculum
Mol Neurobiol, June 2015.
Lunardi N, Oklopcic A, Prillaman M, Erisir A, Jevtovic-Todorovic V.

Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons
Toxicology, June 2015.
Sinner B, Friedrich O, Lindner R, Bundscherer A, Graf BM

Anesthesia-related critical incidents in the perioperative period in children; a proposal for an anesthesia-related reporting system for critical incidents in children
Paediatr Anaesth, June 2015.
De Graaff JC, Sarfo MC, van Wolfswinkel L, van der Werff DB, Schouten AN

Safe Anesthesia For Every Tot – The SAFETOTS initiative.
Curr Opin Anaesthesiol, June 2015. Weiss M, Vutskits L, Hansen TG, Engelhardt T

Surgical Anesthesia in Young Children Linked to Effects on IQ, Brain Structure
Cincinnati Surgical, June 08, 2015

May

Carbon monoxide modulates Cytochrome Oxidase Activity and Oxidative Stress in the Developing Murine Brain During Isoflurane Exposure
Free Radic Biol Med.2015 May 29. pii: S0891-5849(15)00252-X. doi: 10.1016/j.freeradbiomed.2015.05.029. [Epub ahead of print] Cheng Y¹, Mitchell-Flack MJ², Wang A<², Levy RJ

Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes, A Randomized Controlled Trial
Anesthesiology, May 2015. Davidson AJ, Morton NS, Arnup SJ, de Graaff JC, Disma N, Withington DE, Frawley G, Hunt RW, Hardy P, Khotcholava M, von Ungern Sternberg BS, Wilton N, Tuo P, Salvo I, Ormond G, Stargatt R, Locatelli BG, McCann ME

Predictors of Failure of Awake Regional Anesthesia for Neonatal Hernia Repair: Data from the General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes. Anesthesiology. 2015 May 14. Frawley G¹, Bell G, Disma N, Withington DE, de Graaff JC, Morton NS, McCann ME, Arnup SJ, Bagshaw O, Wolfler A, Bellinger D, Davidson AJ; General Anesthesia compared to Spinal anesthesia (GAS) Consortium.

Is this your (paediatric patient’s) brain on (anaesthetic) drugs?: The search for a potential neurological phenotype of anaesthesia-related neurotoxicity in humans
European Journal of Anaesthesiology, May 2015. Loepke AW, Hansen TG.<

Risk of autistic disorder after exposure to general anaesthesia and surgery: A nationwide, retrospective matched cohort study
European Journal of Anaesthesiology, May 2015. Ko WR, Huang JY, Chiang YC, Nfor ON, Ko PC, Jan SR, Lung CC, Chang HC, Lin LY, Liaw YP

Anesthesia and the developing brain: a way forward for clinical research.
Paediatr Anaesth, May 2015. Davidson AJ, Becke K, de Graff J, Giribaldi G, Habre W, Hansen T, Hunt RW, Ing C, Loepke A, McCann ME, Ormond GD, Pini Prato A, Salvo I, Sun L, Vutskits L, Walker S, Disma N.

Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain: A randomised placebo-controlled experimental in-vivo study
Eur J Anaesthesiol, May 2015. Kargaran P, Lenglet S, Montecucco F, Mach F, Copin JC, Vutskits L

Regional anaesthesia in neonates, infants and children: An educational review
European Journal of Anaesthesiology, May 2015. Martin J

Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity
Metab Brain Dis, May 2015. Yi W, Zhang Y, Guo Y, Li D, Li X

April

Only extra-high dose of ketamine affects l-glutamate-induced intracellular Ca2+ elevation and neurotoxicity Neurosci Res, April 2015. Shibuta S, Morita T, Kosaka J, Kamibavashi T, Funino Y

Dexmedetomidine Attenuates Neurotoxicity Induced by Prenatal Propofol Exposure.
J Neurosurg Anesthesiol, April 2015.
Li J, Xiong M, Nadavaluru PR, Zuo W, Ye JH, Eloy JD, Bekker A.

Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood
Anesthesiology, April 2015. Huang L, Yang G

Neurodevelopmental implications of the general anesthesia in neonate and infants
Exp Neurol, April 2015.
Lee JH, Zhang J, Wei L, Yu SP

Neurotoxicity of Generic Anesthesia Agents in Infants and Children: An Orphan Research Question in Search of a Sponsor
JAMA, April 2015. Psaty BM, Platt R, Altman RB

Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.
ASN Neuro. April 2015. Chen C, Shen FY, Zhao X, Zhou T, Xu DJ, Wang ZR, Wang YW

Perioperative effects of caudal and transversus abdominis plane (TAP) blocks for children undergoing urologic robot-assisted laparoscopic surgery.
J Pediatr Urol, April 2015. Faasse MA, Lindgren BW, Frainey BT, Marcus CR, Szczodry DM, Glaser AP, Suresh S, Gong EM

Developmental stage-dependent impact of midazolam on calbindin, calretinin and parvalbumin expression in the immature rat medial prefrontal cortex during the brain growth spurt.
Int J Dev Neurosci, April 2015. Osterop SF, Virtanen MA, Loepke JR, Joseph B, Loepke AW, Vutskits L

Surgical Injury in the Neonatal Rat Alters the Adult Pattern of Descending Modulation from the Rostroventral Medulla
Anesthesiology. 2015 Apr 13. Walker SM, Fitzgerald M, Hathway GJ

Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: a nationwide cohort study
Paediatr Anaesth, February 2015. Hansen TG, Pedersen JK, Henneberg SW, Morton NS, Christensen K

March

Academic Performance After Anesthesia and Surgery During Childhood: A Large-Scale Nation-Wide Study International Anesthesia Research Society, March 23, 2015.

A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia
Paediatr Anaesth, March 2015.

Pre-treatment with a Xingnaojing preparation ameliorates sevoflurane-induced neuroapoptosis in the infant rat striatum.
Mol Med Rep, March 2015.

Effect of apoptosis in neural stem cells treated with sevoflurane
BioMed Central Anesthesiology, 2015.

Neuroprotective effects of pterostilbene against isoflurane-induced apoptosis through regulating the JNK and PI3K/Akt pathway in neonatal rats
Bangladesh Journal of Pharmacology, 2015.

Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood
Anesthesiology, 2015.

Interventional Procedures for Chronic Pain in Children and Adolescents: A Review of the Current Evidence
Pain Pract, March 2015.
Shah RD, Cappiello D, Suresh S

February

Altered Metabolomic Profiles May Be Associated with Sevoflurane-Induced Neurotoxicity in Neonatal Rats. Neurochem Res, February 2015.

Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain.
Pediatr Res, February 2015.

Is There Evidence for Long-Term Neurocognitive Effects of Sedatives
Pediatric Sedation Outside of the Operating Room: A Multispecialty International Collaboration, 2015.

Special aspects of pediatric anesthesia in ophthalmic surgery
Ophthalmologe, February 2015. Keilhauer J, Trieschmann U, Böttiger BW

Morphological features of the neonatal brain following exposure to regional anesthesia during labor and delivery
Magnetic Resonance Imagning, February, 2015

Anesthetic neurotoxicity–clinical implications of animal models
N Engl J Med, February 2015.

January

Hyperexcitability of Rat Thalamocortical Networks after Exposure to General Anesthesia during Brain Development
The Journal of Neuroscience, January 2015.

Molecular pathways of mitochondrial dysfunctions: Possible cause of cell death in anesthesia-induced developmental neurotoxicity.
Brain Res Bull, January 2015.

Pre-administration of curcumin prevents neonatal sevoflurane exposure-induced neurobehavioral abnormalities in mice
Neurotoxicology, January 2015.
Ji MH, Qiu LL, Yang JJ, Zhang H, Sun XR, Zhu SH, Li WY, Yang JJ

Single sevoflurane exposure increases methyl-CpG island binding protein 2 phosphorylation in the hippocampus of developing mice
Mol Med Rep, January 2015.
Han XD, Li M, Zhang XG, Xue ZG, Cang J

Long-term effects of single or multiple neonatal sevoflurane exposures on rat hippocampal ultrastructure
Anesthesiology, January 2015.
Amrock LG, Starner ML, Murphy KL, Baxter MG

2013 Research Articles

December

Anesthesia for the young child undergoing ambulatory procedures: current concerns regarding harm to the developing brain
Curr Opin Anaesthesiol, December 2013.

Do we actually need to anesthetize the neonate?
Pediatric Anesthesia, December 2013.

Early life exposure to sevoflurane impairs adulthood spatial memory in the rat
Neurotoxicology, December 2013.

Modeling anesthetic developmental neurotoxicity using human stem cells
Semin Cardiothorac Vasc Anesth, December 2013.

Neonatal exposure to sevoflurane causes significant suppression of hippocampal long-term potentiation in postgrowth rats.
Anesth Analg, December 2013.

November

A systematic review and quantitative analysis of neurocognitive outcomes in children with four chronic illnesses.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, AB, Canada., November 2013.

October

Educational outcome in adolescence following pyloric stenosis repair before 3 months of age: a nationwide cohort study.
Department of Anesthesia & Intensive Care, Odense University Hospital, Odense C, Denmark. [email protected], October 2013.

Functional implications of an early exposure to general anesthesia: are we changing the behavior of our children?
Mol Neurobiol, October 2013.

September

Basic aspects of the potential toxicity of anesthetic drugs
Arch Pediatr, September 2013.

August

Anesthetic neurotoxicity in the newborn and infant
Department of Anesthesiology and Perioperative Medicine Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR, August 29, 2013.

July

Safety first, safety at early age: The quagmire of neurotoxicity in pediatric anaesthesia
Indian Journal of Anaesthesia, July 25, 2013.

Ketamine as Anesthetics can Damage Children’s Learning and Memory Ability
Science Codex, July 19, 2013.

Long-term effects of neonatal single or multiple isoflurane exposures on spatial memory in rats.
Department of Experimental Psychology, University of Oxford, Oxford , UK ; Glickenhaus Laboratory of Neuropsychology, Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY , USA., July 2013.

June

Cell age-specific vulnerability of neurons to anesthetic toxicity
Department of Anesthesiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; Program in Neuroscience, University of Cincinnati, Cincinnati, OH, June 2013.

May

Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression.
Anesthesiology, May 2013.

April

Propofol-Induced Apoptosis of Neurones and Oligodendrocytes in Fetal and Neonatal Rhesus Macaque Brain
British Journal of Anaesthesia, April 6, 2013.

Characterization and Quantification of Isoflurane-Induced Developmental Apoptotic Cell Death in Mouse Cerebral Cortex
Anesthesia & Analgesia, April 2013.

March

Neonatal Sevoflurane Anesthesia Induces Long-Term Memory Impairment and Decreases Hippocampal PSD-95 Expression without Neuronal Loss
Anesthesiology, March 2013. Department of Anesthesia, ZhongShan hospital, Fudan University, Shanghai, China

February

Prognostic Study of Sevoflurane-Based General Anesthesia on Cognitive Function in Children
J Anesth. 2013 Feb 6. [Epub ahead of print]Neurotoxicity of general anesthetics in childhood: does anesthesia leave its mark on premature babies, newborns and infants?
Anaesthesist, February 2013.

Repeated exposure to propofol potentiates neuroapoptosis and long-term behavioral deficits in neonatal rats.
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, PR China., February 2013.

January

Anesthetics Interfere with Axon Guidance in Developing Mouse Neocortical Neurons In Vitro via a γ-Aminobutyric Acid Type A Receptor Mechanism
Anesthesiology. 2013 Jan 29. [Epub ahead of print]Dual Effects of Isoflurane on Proliferation, Differentiation, and Survival in Human Neuroprogenitor Cells Anesthesiology. 2013 Jan 11. [Epub ahead of print]Sevoflurane Anesthesia in Pregnant Mice Induces Neurotoxicity in Fetal and Offspring Mice
Anesthesiology. 2013 January 9. [epub ahead of print]Selective Anesthesia-induced Neuroinflammation in Developing Mouse Brain and Cognitive Impairment
Anesthesiology. 2013 January 9. [epub ahead of print]Early Developmental Exposure to Volatile Anesthetics Causes Behavioral Defects in Caenorhabditis elegans Anesthesia & Analgesia. January 2013, 116 (1).

2011 Research Articles

December

The abolishment of anesthesia-induced cognitive impairment by timely protection of mitochondria in the developing rat brain: The importance of free oxygen radicals and mitochondrial integrity
Neurobiology of Disease. 2011 Dec 14. [Epub ahead of print] Boscolo A, Starr JA, Sanchez V, Lunardi N, Digruccio MR, Ori C, Erisir A, Trimmer P, Bennett J, Jevtovic-Todorovic V.

Protective Function of Nicotinamide Against Ketamine-induced Apoptotic Neurodegeneration in the Infant Rat Brain
Journal of Molecular Neuroscience. 2011 Dec 8. [Epub ahead of print] Ullah N, Ullah I, Lee HY, Naseer MI, Seok PM, Ahmed J, Kim MO.

November

Anesthetic Neurotoxicity: A Difficult Dragon to Slay
Anesthesia & Analgesia Joss Thomas, Gregory Crosby, John C. Drummond, Michael Todd

Early Childhood Exposure to Anesthesia and Risk of Developmental and Behavioral Disorders in a Sibling Birth Cohort
Anesthesia & Analgesia Dimaggio C, Sun L, Li G

Pediatric Anesthesia Neurotoxicity: An Overview of the 2011 SmartTots Panel
Anesthesia & Analgesia Jevtovic-Todorovic V

SmartTots: A Multidisciplinary Effort to Determine Anesthetic Safety in Young Children
Anesthesia & Analgesia Ramsay JG, Rappaport BA

The Role of Calcium Dysregulation in Anesthetic-Mediated Neurotoxicity
Anesthesia & Analgesia Wei H

The Toxic Effects of S(+)-Ketamine on Differentiating Neurons In Vitro as a Consequence of Suppressed Neuronal Ca2+ Oscillations
Anesthesia & Analgesia Sinner B, Friedrich O, Zink W, Zausig Y, Graf BM

October

Anesthetics and Sedatives: Toxic or Protective for the Developing Brain?
Pharmacological Research [Epub ahead of print] Ward CG, Loepke AW

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery
Pediatrics. [Epub adhead of print] Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO

September

Anesthetic-Related Neurotoxicity and the Developing Brain: Shall We Change Practice?
Paediatric Drugs [Epub ahead of print] Vutskits L

Neurotoxicity of Anesthetic Drugs in the Developing Brain
Anesthesia & Analgesia [Epub ahead of print] Stratmann G

Neonatal Desflurane Exposure Induces More Robust Neuroapoptosis than Do Isoflurane and Sevoflurane and Impairs Working Memory
Anesthesiology [Epub ahead of print] Kodama M, Satoh Y, Otsubo Y, Araki Y, Yonamine R, Masui K, Kazama T

GABAergic Excitotoxicity Injury of the Immature Hippocampal Pyramidal Neurons’ Exposure to Isoflurane Anesthesia & Analgesia [Epub ahead of print] Zhao YL, Xiang Q, Shi QY, Li SY, Tan L, Wang JT, Jin XG, Luo AL

General Anesthesia Causes Long-term Impairment of Mitochondrial Morphogenesis and Synaptic Transmission in Developing Rat Brain
Anesthesiology [Epub ahead of print] Sanchez V, Feinstein SD, Lunardi N, Joksovic PM, Boscolo A, Todorovic SM, Jevtovic-Todorovic V

August

Anesthesia and the developing brain: are we getting closer to understanding the truth?
Current Opinion in Anesthesiology Jevtovic-Todorovic V

Developmental Stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex
Anesthesiology Briner A, Nikonenko I, De Roo M, Dayer A, Muller D, Vutskits L

Propofol induces neuronal apoptosis in infant rat brain under hypoxic conditions
Brain Research Bulletin Tu S, Wang X, Yang F, Chen B, Wu S, He W, Yuan X, Zhang H, Chen P, Wei G

July

Are anaesthetics toxic to the brain?
British Journal of Anaesthesia Hudson AE, Hemmings HC Jr

Disruption of blastomeric F-actin: a potential early biomarker of developmental toxicity in zebrafish Molecular and Cellular Biochemistry Kanungo J, Paule MG

June

Neuraxial labor analgesia for vaginal delivery and its effects on childhood learning disabilities
Anesthesia & Analgesia Flick RP, Lee K, Hofer RE et al.

Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey
Neurotoxicology and Teratology Zuo X, Liu F, Zhang X et al.

Learning disability in children as an outcome in anesthesia and analgesia research
Anesthesia & Analgesia Radcliffe J, Bellinger DC

Developmental stage-dependent persistent impact of propofol anesthesia dendritic spines in the rat medial prefontal cortex
Anesthesiology Briner A, Nikonenko I, De Roo M, Dayer A, Muller D, Vutskits L

Labor analgesia and the developing human brain
Anesthesia & Analgesia Sun LS

May

Academic Performance in Adolescence after Inguinal Hernia Repair in Infancy: A Nationwide Cohort Study Anesthesiology Hansen TG, Pedersen JK, Henneberg SW, Pedersen DA, Murray JC, Morton NS, Christensen K

FDA considers data on potential risks of anesthesia use in infants, children
The Journal of the American Medical Association Kuehn BM

April

Defining safe use of anesthesia in children
The New England Journal of Medicine Rappaport B, Mellon RD, Simone A, Woodcock J

Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys Neurotoxicology and Teratology Paule MG, Li M et al.

2016 Research Articles

December

Obstetricians balk at FDA warning on anesthesia in pregnant women
REUTERS Dec 29, 2016

FDA warns of anesthesia risk in pregnant women, kids under 3
CBS NEWS HEALTHDAY December 15, 2016

Exposure to sevoflurane anesthesia during development does not impair aspects of attention during adulthood in rats
Neurotoxicol Teratol. 2016 Dec 2

Caffeine combined with sedative/anesthetic drugs triggers widespread neuroapoptosis in a mouse model of prematurity
J Matern Fetal Neonatal Med. 2016 Dec 7

Anesthesia Kills Brain Cells, but What Does It Mean?
Anesthesiology Editorial Views December 2016

A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies
Neurotoxicology and Teratology 2016.12.004

November

Association of Anesthesia and Surgery During Childhood With Long-term Academic Performance
JAMA Pediatr. November 7, 2016

The Relevance of Anesthetic Drug-Induced Neurotoxicity
AMA Pediatr. 2016

Review of preclinical studies on pediatric general anesthesia-induced developmental neurotoxicity
Neurotoxicol Teratol. 2016 Nov 18

Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age
Neurochem Res. 2016 Nov 24

Lasting impact of general anesthesia on the brain: mechanism and relevance
Nature Reviews Neuroscience

Anesthetic Neurotoxicity: New Findings and Future Directions
The Journal of Pediatrics

Neonatal inhibition of Na+-K+-2Cl−-cotransporter prevents ketamine induced spatial learning and memory impairments
Neurotoxicology and Teratology 2016.11.01

Isoflurane exposure leads to apoptosis of neurons and oligodendrocytes in 20- and 40-day old rhesus macaques
Neurotoxicology and Teratology 2016.11.06

Anesthetic neurotoxicity: Apoptosis and autophagic cell death mediated by calcium dysregulation
Neurotoxicology and Teratology 2016.11.04

October

Is a short anesthetic exposure in children safe? Time will tell: a focused commentary of the GAS and PANDA trials
Ann Transl Med. 2016 Oct

Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies
Neurotoxicol Teratol. 2016 Oct 26

Minimally invasive biomarkers of general anesthetic-induced developmental neurotoxicity
Neurotoxicology and Teratology 2016.10.07

The genetics of isoflurane-induced developmental neurotoxicity
Neurotoxicology and Teratology 2016.10.07

Neurogenesis and developmental anesthetic neurotoxicity
Neurotoxicology and Teratology 2016.10.01

September

Early-life single-episode sevoflurane exposure impairs social behavior and cognition later in life.
Brain and Behavior

Carbon monoxide and anesthesia-induced neurotoxicity.
Neurotoxicol Teratol. 2016 Sep 9

Astragaloside IV protects new born rats from anesthesia-induced apoptosis in the developing brain.
Exp Ther Med. 2016 Sep;12

Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.
Rev Bras Anestesiol. 2016

Long-lasting behavioral effects in neonatal mice with multiple exposures to ketamine-xylazine anesthesia.
Neurotoxicol Teratol. 2016 Sep 10

Altered hippocampal microRNA expression profiles in neonatal rats caused by sevoflurane anesthesia: MicroRNA profiling and bioinformatics target analysis.
Exp Ther Med. 2016 Sep;12

Long-term Fate Mapping to Assess the Impact of Postnatal Isoflurane Exposure on Hippocampal Progenitor Cell Productivity
Anesthesiology 2016 Sep 21

The effect of anaesthesia on the infant brain
Early Hum Dev. 2016 Sep 10

Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years
26 September 2016

August

Role of mitochondrial complex I and protective effect of CoQ10 supplementation in propofol induced cytotoxicity
Journal of Bioenergetics and Biomembranes August 2016

June

General anesthetics and cytotoxicity: possible implications for brain health.
Drug and Chemical Toxicology. June 2, 2016

May

Cognitive Dysfunction in Children with Heart Disease: The Role of Anesthesia and Sedation
Congenital Heart Disease, May/June 2016

April

Multiple sevoflurane exposures in infant monkeys do not impact the mother-infant bond
Neurotoxicology and Teratology, April 2016

Ketamine exposure during embryogenesis inhibits cellular proliferation in rat fetal cortical neurogenic regions
Acta Anaesthesiologica Scandinavica, April 2016

Paediatric anaesthesia and neurotoxicity: can we translate findings from animals to humans?
Minerva Anestesiologica, April 2016

Oral Clefts and Academic Performance in Adolescence: The Impact of Anesthesia-Related Neurotoxicity, Timing of Surgery, and Type of Oral Clefts
Cleft Palate Craniofac J., April 2016

Increasing cumulative exposure to volatile anesthetic agents is associated with poorer neurodevelopmental outcomes in children with hypoplastic left heart syndrome.
J Thorac Cardiovasc Surg., April 2016

rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes
J Neurochem, April 2016

Xenon depresses aEEG background voltage activity whilst maintaining cardiovascular stability in sedated healthy newborn pigs
J Neurol Sci. April 2016

March

A lasting effect of postnatal sevoflurane anesthesia on the composition of NMDA receptor subunits in rat prefrontal cortex
International Journal of Developmental Neuroscience, March 2016

Potential neurotoxicity of anesthetic drugs in young children: who cares? A survey among European anesthetists
Minerva Anestesiologica, March 2016

Preterm Versus Term Children: Analysis of Sedation/Anesthesia Adverse Events and Longitudinal Risk
Pediatrics, March 2016

Neuronal apoptosis may not contribute to the long-term cognitive dysfunction induced by a brief exposure to 2% sevoflurane in developing rats
Biomedicine & Pharmacotherapy, March 2016

Lithium Protects Against Anesthesia Neurotoxicity in the Infant Primate Brain
Scientific Reports, March 2016

Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain
The Journal of Maternal-Fetal & Neonatal Medicine, March 2016

The mitochondrial division inhibitor Mdivi-1 rescues mammalian neurons from anesthetic-induced cytotoxicity
Mol Brain, March 2016

February

Ensuring safe anaesthesia for neonates, infants and young children: what really matters
Archives of Disease in Childhood, February, 2016

Inflammation Increases Neuronal Sensitivity to General Anesthetics.
Anesthesiology, February 2016.

Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3β Signaling Pathway
BioMed Research International, February, 2016

January

The rise and fall of anaesthesia-related neurotoxicity and the immature developing human brain
Acta Anaesthesiologica Scandinavica, January, 2016

Increased mitochondrial ATP production capacity in brain of healthy mice and a mouse model of isolated complex I deficiency after isoflurane anesthesia
Journal of Inherited Medicine, January 2016

Acute and Long-Term Effects of Brief Sevoflurane Anesthesia During the Early Postnatal Period in Rats
Toxicol. Sci., January 2016

α-Lipoic acid inhibits sevoflurane-induced neuronal apoptosis through PI3K/Akt signalling pathway
Cell Biochemistry and Function, January 2016

Midazolam dose correlates with abnormal hippocampal growth and neurodevelopmental outcome in preterm infants
Annals of Neurology, January 2016

Differential Suppression of Spontaneous and Noxious-evoked Somatosensory Cortical Activity by Isoflurane in the Neonatal Rat
Anesthesiology, January 2016

Etomidate exposure in early infant mice does not induce apoptosis or affect behavior
Acta Anaesthesiol Scand, January 2016

2014 Research Articles

December

Neurodevelopment of children exposed to anesthesia: Design of the Mayo Anesthesia Safety in Kids (MASK) study
Contemp Clin Trials, December 2014.

Propofol inhibits proliferation and induces neuroapoptosis of hippocampal neurons in vitro via downregulation of NF-κB p65 and Bcl-2 and upregulation of caspase-3
Cell Biochem Funct, December 2014.

November

Are Caudal Blocks for Pain Control Safe in Children? An Analysis of 18,650 Caudal Blocks from the Pediatric Regional Anesthesia Network (PRAN) Database.
Anesthesia & Analgesia, November 2014.

Vitamin C Attenuates Isoflurane-Induced Caspase-3 Activation and Cognitive Impairment
Molecular Neurobiology, November 2014.

October

Anesthesia in Children: Perspectives From Nonsurgical Pediatric Specialists
Journal of Neurosurgical Anesthesiology, October 2014.

Clinical Research Into Anesthetic Neurotoxicity: Does Anesthesia Cause Neurological Abnormalities in Humans?
Journal of Neurosurgical Anesthesiology, October 2014.

Engaging Stakeholders in Research Related to Anesthesia and Neurodevelopment in Children
Journal of Neurosurgical Anesthesiology, October 2014.

Isoflurane Impairs the Capacity of Astrocytes to Support Neuronal Development in a Mouse Dissociated Coculture Model
Journal of Neurosurgical Anesthesiology, October 2014.

Ketamine Affects the Neurogenesis of Rat Fetal Neural Stem Progenitor Cells via the PI3K/Akt-p27 Signaling Pathway.
Birth defects research. Part B, Developmental and reproductive toxicology, October 2014.

Neurodevelopmental Outcomes After Initial Childhood Anesthetic Exposure Between Ages 3 and 10 Years Journal of Neurosurgical Anesthesiology, October 2014.

Pediatric Surgeons and Anesthesiologists Expand the Dialogue on the Neurotoxicity Question, Rationale for Early and Delayed Surgeries, and Practice Changes While Awaiting Definitive Evidence
Journal of Neurosurgical Anesthesiology, October 2014.

Postoperative Cognitive Function Following General Versus Regional Anesthesia: A Systematic Review Journal of Neurosurgical Anesthesiology, October 2014.

Report of the Fourth PANDA Symposium on Anesthesia and Neurodevelopment in Children Journal of Neurosurgical Anesthesiology, October 2014.

Review: effects of anesthetics on brain circuit formation.
Journal of Neurosurgical Anesthesiology, October 2014.

September

Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children.
Paediatric Anaesthesia, September 2014.

Cognitive Outcomes After Infant Spinal Anesthesia: The Other Side of the Coin
Anesthesia & Analgesia, September 2014.

Neurosurgical conditions and procedures in infancy are associated with mortality and academic performances in adolescence: a nationwide cohort study
Pediatric Anesthesia, September 2014.

Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3β activation in young mice
Anesthesiology, September 2014.

August

Anesthetic Preconditioning Inhibits Isoflurane-Mediated Apoptosis in the Developing Rat Brain.
Anesthesia & Analgesia, Aug. 5, 2014.

Long term neurotoxicity by general anesthetics in infants
Anaesthesia, Pain & Intensive Care, 2014.

July

Role of miR-34c in ketamine-induced neurotoxicity in neonatal mice hippocampus
Cell Biol Int., July 23, 2014.

Both JNK and P38 MAPK pathways participate in the protection by dexmedetomidine against isoflurane-induced neuroapoptosis in the hippocampus of neonatal rats.
Brain Res Bull, July 2014.

Dexmedetomidine provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain
Acta Anaesthesiol Scand, July 2014.

Down-regulation of MicroRNA-21 Is Involved in the Propofol-induced Neurotoxicity Observed in Human Stem Cell-derived Neurons.
Anesthesiology, July 2014.

Endocrine and Neurobehavioral Abnormalities Induced by Propofol Administered to Neonatal Rats.
Anesthesiology, July 2014.

Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity Pediatric Anesthesia, July 2014.

June

Neonatal Anesthesia Neurotoxicity: A Review for Cleft and Craniofacial Surgeons
The Cleft Palate-Craniofacial Journal, June 18, 2014.

Cognitive Outcome after Spinal Anesthesia and Surgery During Infancy
Anesthesia & Analgesia, June 2014.

Comparison of neurodegeneration and cognitive impairment in neonatal mice exposed to propofol or isoflurane.
PLoS One, June 2014.

Effect of General Anesthesia in Infancy on Long-Term Recognition Memory in Humans and Rats
Neuropsychopharmacology, June 2014.

Impact of ketamine on learning and memory function, neuronal apoptosis and its potential association with miR-214 and PTEN in adolescent rats.
PLoS One, June 2014.

The Neonatologist’s Role in Pediatric Anesthesia Neurotoxicity
JAMA Pediatrics, June 2014.

May

The role of miR-124 in modulating hippocampal neurotoxicity induced by ketamine anesthesia
International Journal of Neuroscience, May 13, 2014.

General anaesthetics and the developing brain: an overview.
Anaesthesia, May 14, 2014.

Propofol anesthesia induces proapoptotic tumor necrosis factor-α and pro-nerve growth factor signaling and prosurvival Akt and XIAP expression in neonatal rat brain.
J Neurosci Res, May 14, 2014.

Repeated Administration of Ketamine can Induce Hippocampal Neurodegeneration and Long-Term Cognitive Impairment via the ROS/HIF-1α Pathway in Developing Rats.
Cell Physiol Biochem, May 2014.

Neurotoxic effects of dexmedetomidine in fetal cynomolgus monkey brains
J Toxicol Sci, 2014.

April

Ketamine administered to pregnant rats in the second trimester causes long-lasting behavioral disorders in offspring.
Neurobiol Dis, April 26, 2014.

Comparative Analysis of Outcome Measures Used in Examining Neurodevelopmental Effects of Early Childhood Anesthesia Exposure
Anesthesiology, April 2014.

Dexmedetomidine Reduces Isoflurane-Induced Neuroapoptosis Partly by Preserving P13K/Akt Pathway in the Hippocampus of Neonatal Rats
PLoS One, April 2014.

Dual effects of ketamine: neurotoxicity versus neuroprotection in anesthesia for the developing brain
J Neurosurg Anesthesiol, April 2014.

Involvement of RAGE in isoflurane-induced neuronal apoptosis
The FASEB Journal, April 2014.

Isoflurane exposure in newborn rats induces long-term cognitive dysfunction in males but not females Neuropharmacology, April 2014.

Neuroprotective gases–fantasy or reality for clinical use?
Prog Neurobiol, April 2014.

Sevoflurane in combination with propofol, not thiopental, induces a more robust neuroapoptosis than sevoflurane alone in the neonatal mouse brain
Journal of Anesthesia, April 2014.

The role of miR-21 in propofol-induced neurotoxicity in developing human neurons (1093.2)
The FASEB Journal, April 2014.

March

Inhibition of Acetylcholinesterase Modulates NMDA Receptor Antagonist Mediated Alterations in the Developing Brain
Int. J. Mol. Sci., March 3, 2014.

Repeated Exposure to Anesthetic Ketamine Can Negatively Impact Neurodevelopment in Infants: A Prospective Preliminary Clinical Study.
J Child Neurol, March 20, 2014.

Anesthesia considerations in pediatric glaucoma management
Curr Opin Ophthalmol, March 2014.

Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence
Brain Sci, March 2014.

Anesthetic neurotoxicity
Anesthesiol Clin, March 2014.

Exposure to general anesthesia in early life and the risk of attention deficit/hyperactivity disorder development: a nationwide, retrospective matched-cohort study
Paediatr Anaesth, March 2014.

Inflammation and the developing brain: consequences for hippocampal neurogenesis and behavior.
Neurosci Biobehav Rev., March 2014.

Isoflurane-induced Apoptosis of Neurons and Oligodendrocytes in the Fetal Rhesus Macaque Brain
Anesthesiology, March 2014.

Neonatal Morphine in Extremely and Very Preterm Neonates: Its Effect on the Developing Brain, a Review
J Matern Fetal Neonatal Med, March 2014.

The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study.
Paediatr Anaesth, March 2014.

The potential dual effects of sevoflurane on AKT/GSK3beta signaling pathway
Med Gas Res, March 2014.

February

Adverse effect of inhalational anesthetics on the developing brain
Med Gas Res, February 2014.

Anesthesia and the Developing Brain: Relevance to the Pediatric Cardiac Surgery
Brain Sci, February 2014.

Inhibition of aberrant cyclin-dependent kinase 5 activity attenuates isoflurane neurotoxicity in the developing brain
Neuropharmacology, February 2014.

January

Brain regional vulnerability to anaesthesia-induced neuroapoptosis shifts with age at exposure and extends into adulthood for some regions
Br. J. Anaesth, January 2014.

Physiological disturbance may contribute to neurodegeneration induced by isoflurane or sevoflurane in 14 day old rats
PLoS One, January 2014.

Subclinical Carbon Monoxide Limits Apoptosis in the Developing Brain After Isoflurane Exposure
Anesth Analg, January 2014.

2012 Research Articles

December

Perioperative Central Nervous System Injury in Neonates
British Journal of Anaesthesia. 2012 Dec;109 Suppl 1. McCann ME, Soriano SG.

Early Developmental Exposure to Volatile Anesthetics Causes Behavioral Defects in Caenorhabditis elegans Anesth Analg. 2012 Dec 7. [Epub ahead of print] Gentry KR, Steele LM, Sedensky MM, Morgan PG.

November

Newly Postulated Neurodevelopmental Risks of Pediatric Anesthesia: Theories That Could Rock Our World The Journal of Urology. J Urol. 2012 Nov 20. [Epub ahead of print] Hays SR, Deshpande JK.

October

Preclinical research into the effects of anesthetics on the developing brain: promises and pitfalls
J Neurosurg Anesthesiol. 2012 Oct;24(4):362-7. Mintz CD, Wagner M, Loepke AW.

Anesthetics interfere with the polarization of developing cortical neurons
J Neurosurg Anesthesiol. 2012 Oct;24(4):368-75. Mintz CD, Smith SC, Barrett KM, Benson DL.

Isoflurane-induced apoptosis of oligodendrocytes in the neonatal primate brain
Ann Neurol. 2012 Oct;72(4):525-35. Brambrink AM, Back SA, Riddle A, Gong X, Moravec MD, Dissen GA, Creeley CE, Dikranian KT, Olney JW.

Report of the third PANDA symposium on “Anesthesia and Neurodevelopment in Children”
J Neurosurg Anesthesiol. 2012 Oct;24(4):357-61. Miller TL, Park R, Sun LS.

Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project
J Neurosurg Anesthesiol. 2012 Oct;24(4):382-8. Sun LS, Li G, DiMaggio CJ, Byrne MW, Ing C, Miller TL, Bellinger DC, Han S, McGowan FX.

Elective procedures and anesthesia in children: pediatric surgeons enter the dialogue on neurotoxicity questions, surgical options, and parental concerns
J Neurosurg Anesthesiol. 2012 Oct;24(4):396-400. Byrne MW, Ascherman JA, Casale P, Cowles RA, Gallin PF, Maxwell LG.

Pediatric anesthesia and neurodevelopmental impairments: a Bayesian meta-analysis
J Neurosurg Anesthesiol. 2012 Oct;24(4):376-81. DiMaggio C, Sun LS, Ing C, Li G.

Anesthesia-Induced Developmental Neurodegeneration: The Role of Neuronal Organelles
Front Neurol. 2012; 3: 141. Published online 2012 October 11. doi: 10.3389/fneur.2012.00141 Vesna Jevtovic-Todorovic, A. Boscolo, V. Sanchez, N. Lunardi

Advanced pre-clinical research approaches and models to studying pediatric anesthetic neurotoxicity
Front Neurol. 2012;3:142. doi: 10.3389/fneur.2012.00142. Epub 2012 Oct 17. Wang C.

SmartTots: A Public-Private Partnership Between the United States Food and Drug Administration (FDA) and the International Anesthesia Research Society (IARS)
Paediatr Anaesth. 2012 Oct;22(10):969-72. Ramsay JG, Roizen M, Davidson A

September

Propofol at Clinically Relevant Concentrations Increases Neuronal Differentiation But Is Not Toxic to Hippocampal Neural Precursor Cells In Vitro
Anesthesiology. 2012 Sep 20. [Epub ahead of print] Sall JW, Stratmann G, Leong J, Woodward E, Bickler PE

Neonatal Exposure to Sevoflurane Causes Apoptosis and Reduces nNOS Protein Expression in Rat Hippocampus
Mol Med Report. 2012 Sep;6(3):543-6. doi: 10.3892/mmr.2012.976. Epub 2012 Jul 2. Zhou X, Song FH, He W, Yang XY, Zhou ZB, Feng X, Zhou LH.

Are Anesthesia and Surgery during Infancy Associated with Altered Academic Performance during Childhood?
Anesthesiology. 2012 Sep;117(3):494-503. Block RI, Thomas JJ, Bayman EO, Choi JY, Kimble KK, Todd MM.

Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia Pediatrics. 2012 Sep;130(3):e476-85. Ing C, Dimaggio C, Whitehouse A, Hegarty MK, Brady J, von Ungern-Sternberg BS, Davidson A, Wood AJ, Li G, Sun LS.

Review Article: Neuraxial Analgesia in Neonates and Infants: A Review of Clinical and Preclinical Strategies for the Development of Safety and Efficacy Data
Anesthesia & Analgesia. 2012 Sep;115(3):638-62. Epub 2012 Jul 13. Walker SM, Yaksh TL.

August

General Anesthesia: A Gateway to Modulate Synapse Formation and Neural Plasticity?
Vutskits L Anesthesia & Analgesia. 2012 Aug 2. [Epub ahead of print]

March

Neurotoxicity and the need for anesthesia in the newborn: Does the emperor have no clothes?
Anesthesiology. 2012 Mar;1

Delayed environmental enrichment reverses sevoflurane-induced memory impairment
Anesthesiology. 2012 Mar;1

Maternal anesthesia and fetal neurodevelopment
Int J Obstet Anesth. 2012

February

Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia Mayo Clinic Proceedings. 2012 Feb;87(2):120-9. Sprung J, Flick RP, Katusic SK, Colligan RC, Barbaresi WJ, Bojanić K, Welch TL, Olson MD, Hanson AC, Schroeder DR, Wilder RT, Warner DO.
Propofol Neurotoxicity Is Mediated by p75 Neurotrophin Receptor Activation

Anesthesiology. Pearn, Matthew L. M.D.; Hu, Yue B.S.; Niesman, Ingrid R. M.S.; Patel, Hemal H. Ph.D.; Drummond, John C. M.D.; Roth, David M. Ph.D., M.D.; Akassoglou, Katerina Ph.D.; Patel, Piyush M. M.D.; Head, Brian P. M.S., Ph.D.

January

Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain
Anesthesiology. 2012 Jan 4. [Epub ahead of print] Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Martin LD, Dissen GA, Creeley CE, Olney JW.

2009 Research Articles

May

Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats.
Anesthesiology, May 2009.