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Anesthetic neurotoxicity

Dongdong Chai, Hong Jiang, Qifang Li
OBJECTIVE: Previously, we found that the inhaled anesthetic isoflurane up-regulated the transcriptional factor hypoxia inducible factor (HIF)-1α protein levels during induction of neurodegeneration in the brain of neonatal rats. Here, we investigated the role of HIF-1α and the underlying signaling pathway in the neurodegenration induced by isoflurane in rodent developing brain. METHODS: Primary hippocampal neurons were exposed to isoflurane (0.4mM) for 12h. Neuron injury was analyzed by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetra-zolium bromide (MTT) test and quantification of lactate dehydrogenaserelease...
October 18, 2016: Brain Research
Riva R Ko, Teeda Pinyavat, Steven Stylianos, Sarah M Lambert, Richard C Anderson, Pamela F Gallin, Lynne G Maxwell, Christopher G Ward, Jayant K Deshpande, Constance S Houck
The Pediatric Anesthesia Neuro Development Assessment (PANDA) team at the Anesthesiology Department at Columbia University Medical Center held its fifth biennial symposium to discuss issues regarding potential neurotoxicity of anesthetic agents in pediatric patients. Overall optimal surgical timing as well as a "critical window" for surgery on a specialty specific basis are areas of focus for the American Academy of Pediatrics Surgical Advisory Panel. An ad hoc panel of pediatric surgical experts representing general surgery, urology, neurosurgery, and ophthalmology was assembled for this meeting and provided a dialogue focused on the benefits of early intervention versus potential anesthetic risk, addressing parental concerns, and the need for continued interdisciplinary collaboration in this area...
October 2016: Journal of Neurosurgical Anesthesiology
Teeda Pinyavat, David O Warner, Randall P Flick, Mary Ellen McCann, Dean B Andropoulos, Danquig Hu, Jeffrey W Sall, Marisa N Spann, Caleb Ing
During the Fifth Pediatric Anesthesia Neurodevelopmental Assessment Symposium, experts and stakeholders met to present and discuss recent advances made in the study of neurodevelopmental outcomes after exposure to anesthetic drugs in infants and children. This article summarizes the update of 5 ongoing clinical studies: General Anesthesia compared to Spinal Anesthesia, Toxicity of Remifentanil and Dexmedetomidine, Mayo Anesthesia Safety in Kids, the University of California San Francisco human cohort study, and Columbia University Medical Center Neonatal Magnetic Resonance Imaging study...
October 2016: Journal of Neurosurgical Anesthesiology
Tonya L K Miller, Raymond Park, Lena S Sun
On April 16 and 17, 2016, the Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study held its fifth biennial symposium at the Morgan Stanley Children's Hospital of New York. The PANDA symposium has served as a key forum for clinicians, researchers, and other major stakeholders to gather and review the current state of preclinical and clinical research related to anesthetic neurotoxicity in children. Goals of the meeting included assessing how current knowledge has translated and impacted clinical care of patients who may be at risk, and future directions for research and policy...
October 2016: Journal of Neurosurgical Anesthesiology
Mary Ellen McCann, Jurgen de Graaff
PURPOSE OF REVIEW: Numerous preclinical studies have shown that general anesthetics adversely influence on the development of young brains. These adverse effects are dose-dependent occurring in specific stages of brain development. Histologic examinations show increased apoptosis, pathological neurogenesis and dendritic formation after exposure of infant animals to virtually all general anesthetics at a clinically effective dose which are associated with memory and behavioral changes at adulthood...
October 15, 2016: Current Opinion in Urology
Eunchai Kang, Daniel A Berg, Orion Furmanski, William M Jackson, Yun Kyoung Ryu, Christy D Gray, C David Mintz
The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure...
October 14, 2016: Neurotoxicology and Teratology
Bin Liu, Junming Xia, Yali Chen, Jun Zhang
Neonatal exposure to volatile anesthetics causes apoptotic neurodegeneration in the developing brain, possibly leading to neurocognitive deficits in adulthood. Endoplasmic reticulum (ER) stress might be associated with sevoflurane (sevo)-induced neuroapoptosis. However, the signaling pathway regulating sevo-induced neuroapoptosis is not understood. We investigated the effects of neonatal sevo exposure on ER signaling pathway activation. Seven-day-old mouse pups were divided into control (C) and sevo (S; 3 % sevo exposure, 6 h) groups...
September 28, 2016: Neurotoxicity Research
Tianchao Yu, Wanchun Lin
BACKGROUND: Application of general anesthetics may induce neurotoxicity in dorsal root ganglia (DRG) neurons. In this study, we examined the possible protective mechanism and associated signaling pathways of small-molecule glycogen synthase kinase-3 (GSK-3) inhibitor, SB216763, in bupivacaine-injured mouse DRG neurons in vitro. METHODS: In vitro DRG explant of 6-week old mice was treated with 5mM bupivacaine to induce neurotoxicity. The explants were also pre-treated with SB216763 for 72h...
September 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Victoria J Forster, Frederik W van Delft, Susan F Baird, Shona Mair, Roderick Skinner, Christina Halsey
PURPOSE: Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity. METHODS: We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy...
September 22, 2016: Cancer Chemotherapy and Pharmacology
Elham Memari, Mohammad-Ali Hosseinian, Ali Mirkheshti, Ali Arhami-Dolatabadi, Mojtaba Mirabotalebi, Mohsen Khandaghy, Yahya Daneshbod, Leila Alizadeh, Sadegh Shirian
Injection of a variety of drugs such as local anesthetics (LAs) for peripheral nerve block has been shown to cause damage to peripheral nerves. Bupivacaine is a local anesthetic widely used in surgical procedures. The aim of this study was to evaluate the neurotoxicity of LAs including Bupivacaine and dexmedetomidine (DEX)-Bupivacaine on sciatic nerve tissue at histopathological level. In addition, we investigated whether perineural administration of DEX can attenuate Bupivacaine-induced neurotoxicity. Twenty adult Sprague Dawley rats received unilateral sciatic nerve blocks with either 0...
September 17, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Richard J Levy
The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria...
September 9, 2016: Neurotoxicology and Teratology
Jishi Ye, Zongze Zhang, Yanlin Wang, Chang Chen, Xing Xu, Hui Yu, Mian Peng
Although accumulating evidence has suggested that microRNAs (miRNAs) have a serious impact on cognitive function and are associated with the etiology of several neuropsychiatric disorders, their expression in sevoflurane-induced neurotoxicity in the developing brain has not been characterized. In the present study, the miRNAs expression pattern in neonatal hippocampus samples (24 h after sevoflurane exposure) was investigated and 9 miRNAs were selected, which were associated with brain development and cognition in order to perform a bioinformatic analysis...
September 2016: Experimental and Therapeutic Medicine
Chunsheng Feng, Ya Liu, Ye Yuan, Weiwei Cui, Feng Zheng, Yuan Ma, Meihua Piao
Zinc (Zn) is known to play crucial roles in numerous brain functions including learning and memory. Zn deficiency is believed to be widespread throughout the world, particularly in patients with Alzheimer's disease (AD). A number of studies have shown that volatile anesthetics, such as isoflurane, might be potential risk factors for the development of AD. However, whether isoflurane exposure accelerates the process of AD and cognitive impairment in AD patients with Zn deficiency is yet to be documented. The aim of the present study was to explore the effects of 1...
December 2016: Neuropharmacology
Caleb Ing, Virginia A Rauh, David O Warner, Lena S Sun
On April 16 and 17, 2016, the Fifth biennial Pediatric Anesthesia & Neurodevelopment Assessment (PANDA) symposium was convened at the Morgan Stanley Children's Hospital of New York at Columbia University Medical Center. During the symposium, experts in the fields of anesthesiology, neuropsychology, and epidemiology were convened in a small group session to determine the level of confidence in the current clinical evidence and the next steps in anesthetic neurotoxicity clinical research. Among the participants in the discussion, there remained a lack of consensus on whether anesthetic exposure causes long-term neurodevelopmental deficits in children based on the current evidence...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Yolanda Y Huang, Lucy Li, Matthew Monteleone, Lynne Ferrari, Lisa J States, James J Riviello, Steven G Kernie, Ali A Mencin, Sumit Gupta, Lena S Sun
Ongoing investigation from the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) study hopes to examine the long-term effect on cognitive and language development of a single anesthetic exposure in children undergoing inguinal hernia repair. The fifth PANDA Symposium, held in April 2016, continued the mission of previous symposia to examine evidence from basic science and clinical studies on potential neurotoxic effects of anesthetics on developing brain. At the 2016 Symposium, a panel of specialists from nonsurgical pediatric disciplines including anesthesiology, radiology, neurology, gastroenterology, oncology, cardiology, and critical care reviewed use of anesthesia in their practices, including how concern over possible neurodevelopmental effects of early childhood anesthetic exposure has changed discussion with patients and families regarding risks and benefits of imaging studies and interventional procedures involving sedation or anesthesia...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Yolanda Y Huang, Caleb Ing, Gouhua Li, Lena S Sun
INTRODUCTION: Although animal studies have consistently demonstrated long-term neurocognitive deficits following early anesthetic exposure under certain conditions, risk in human children remains unknown. Magnetic resonance imaging (MRI) in young patients often requires anesthesia to facilitate image acquisition. We studied MRI utilization in a pediatric population, and associated use of anesthesia for ambulatory MRI. MATERIALS AND METHODS: Data were obtained from the New York State Inpatient Database and State Ambulatory Surgery and Services Database on MRI performed in children under the age of 18 years from 2005 to 2011...
August 25, 2016: Journal of Neurosurgical Anesthesiology
William M Jackson, Christy D B Gray, Danye Jiang, Michele L Schaefer, Caroline Connor, Cyrus D Mintz
Data from epidemiologic studies and animal models have raised a concern that exposure to anesthetic agents during early postnatal life may cause lasting impairments in cognitive function. It is hypothesized that this is due to disruptions in brain development, but the mechanism underlying this toxic effect remains unknown. Ongoing research, particularly in rodents, has begun to address this question. In this review we examine currently postulated molecular mechanisms of anesthetic toxicity in the developing brain, including effects on cell death pathways, growth factor signaling systems, NMDA and GABA receptors, mitochondria, and epigenetic factors...
October 2016: Journal of Neurosurgical Anesthesiology
Richard J Levy, Julie B Herbstman, Zeljko J Bosnjak, Andreas W Loepke, Francis X McGowan
Exposure to commonly used anesthetic agents causes widespread neuronal degeneration in the developing mammalian brain and has been shown to impair neurodevelopment in a variety of newborn vertebrate animal species. Although retrospective studies have suggested an association between anesthesia exposure in childhood and subsequent neurodevelopmental abnormalities, a causal relationship in humans has yet to be demonstrated. Unfortunately, translation of findings from bench to bedside is limited by several factors and histologic assessment in healthy children following exposure to anesthesia is not possible...
August 25, 2016: Journal of Neurosurgical Anesthesiology
Matthias Görges, Nicholas C West, Edda Karlsdóttir, J Mark Ansermino, Myles Cassidy, Gillian R Lauder
BACKGROUND: Commonly used general anesthetics are considered to be neurotoxic to the developing rodent brain, leading to poor long-term outcome. However, it is unclear whether these rodent studies can be extrapolated to the human neonate. Given that anesthesia for urgent neonatal surgery cannot be avoided, it is vitally important to assess other factors that may impact neurological outcome following anesthesia and surgery. OBJECTIVE: The purpose of this study is to identify thresholds for detecting vital sign deviations, which may have the potential for affecting neurological outcome following anesthesia and surgery in neonates...
November 2016: Paediatric Anaesthesia
Zeljko J Bosnjak, Sarah Logan, Yanan Liu, Xiaowen Bai
Mounting evidence has demonstrated that general anesthetics could induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long-term memory and learning abnormalities. Propofol is a commonly used intravenous anesthetic agent for the induction and maintenance of anesthesia and procedural and critical care sedation in children. Compared with other anesthetic drugs, little information is available on its potential contributions to neurotoxicity. Growing evidence from multiple experimental models showed a similar neurotoxic effect of propofol as observed in other anesthetic drugs, raising serious concerns regarding pediatric propofol anesthesia...
August 22, 2016: Anesthesia and Analgesia
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