Comparison of the Neuroapoptotic Properties of Equipotent Anesthetic Concentrations of Desflurane, Isoflurane, or Sevoflurane in Neonatal Mice
ABSTRACT Volatile anesthetics facilitate surgical procedures and imaging studies in millions of children every year. Neuronal cell death after prolonged exposure to isoflurane in developing animals has raised serious concerns regarding its safe use in children. Although sevoflurane and desflurane are becoming more popular for pediatric anesthesia, their cytotoxic effects have not been compared with those of isoflurane. Accordingly, using newborn mice, the current study established the respective potencies of desflurane, isoflurane, and sevoflurane and then compared equipotent doses of these anesthetics regarding their effects on cortical neuroapoptosis.
Minimum alveolar concentrations were determined in littermates (aged 7-8 days, n = 42) using tail-clamp stimulation in a bracketing study design. By using equipotent doses of approximately 0.6 minimum alveolar concentration, another group of littermates was randomly assigned to receive desflurane, isoflurane, or sevoflurane or to fast in room air for 6 h. After exposure, animals (n = 47) were euthanized, neocortical apoptotic neuronal cell death was quantified, and caspase 3 activity was compared between the four groups.
The minimum alveolar concentration was determined to be 12.2% for desflurane, 2.7% for isoflurane, and 5.4% for sevoflurane. After a 6-h exposure to approximately 0.6 minimum alveolar concentration of desflurane, isoflurane, or sevoflurane, neuronal cell death and apoptotic activity were significantly increased, irrespective of the specific anesthetic used.
In neonatal mice, equipotent doses of the three commonly used inhaled anesthetics demonstrated similar neurotoxic profiles, suggesting that developmental neurotoxicity is a common feature of all three drugs and cannot be avoided by switching to newer agents.
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ABSTRACT: The assumption that anesthesia has no serious, long-term, adverse central nervous system consequences may be true for most patients between 6 months and 60 years of age. However, for patients younger than 6 months or older than 60 years, that status quo assumption is under challenge from a growing body of evidence. Fetuses and newborns appear to be at risk because systems that would enable them to fully recover from the effects of more than 2 hours of anesthesia are still in development. In distinction, the elderly appear to be at risk because systems that once enabled them to fully recover have ever-diminishing capacity. Even for those between the age of 6 months and 60 years, full recovery may require replacing apoptosed neurons and pruning overabundant dendritic spines…perhaps leaving patients not quite the same person that they were before they were anesthetized.Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine 01/2012; 79(1):75-94. DOI:10.1002/msj.21283 · 1.56 Impact Factor
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ABSTRACT: Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks. © The Author(s) 2015.ASN Neuro 04/2015; 7(2). DOI:10.1177/1759091415575845 · 4.44 Impact Factor
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ABSTRACT: With growing evidence that anesthesia exposure in infancy affects cognitive development, it is important to understand how distinct anesthetic agents and combinations can alter long-term memory. Investigations of neuronal death suggest that combining anesthetic agents increases the extent of neuronal injury. However, it is unclear how the use of simultaneously combined anesthetics affects cognitive outcome relative to the use of a single agent.International Journal of Developmental Neuroscience 07/2014; 37. DOI:10.1016/j.ijdevneu.2014.06.016 · 2.92 Impact Factor