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Open AccessJournal ArticleDOI

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

TLDR
mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes, however, definitive clinical data remain elusive.
Abstract
Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches.

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Clinical Pharmacokinetics and Pharmacodynamics of Propofol.

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Anesthetic Neurotoxicity — Clinical Implications of Animal Models

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Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

TL;DR: Findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention.
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Executive Function in Children and Adolescents with Critical Cyanotic Congenital Heart Disease

TL;DR: With increased understanding of the cognitive and self-regulatory vulnerabilities experienced by children and adolescents with CHD, it may be possible to identify risks early and provide individualized supports to promote optimal neurodevelopment.
References
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Journal ArticleDOI

Isoflurane impairs immature astroglia development in vitro: the role of actin cytoskeleton.

TL;DR: Isoflurane-induced actin cytoskeletal changes were accompanied by a significant decrease in protein levels of the endogenous GTPase RhoA that regulates the phosphorylation of myosin light chain protein, suggesting that isoflurane -induced impairment in glial growth and morphological development is, in part, mediated by the RHoA/myosinLight chain protein signaling pathway.
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Heat Shock Protein 72 Overexpression Prevents Early Postoperative Memory Decline after Orthopedic Surgery under General Anesthesia in Mice

TL;DR: Hsp72 overexpression is associated with prevention of postoperative hippocampal-dependent and -independent memory deficit induced by anesthesia and/or surgery and is not correlated with numbers of activated hippocampal microglia.
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Isoflurane Preconditioning Elicits Competent Endogenous Mechanisms of Protection from Oxidative Stress in Cardiomyocytes Derived from Human Embryonic Stem Cells

TL;DR: The results suggest a promising ability of APC to protect and improve engraftment of hESC-derived cardiomyocytes into the ischemic heart and potentially other treatments/diseases.
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Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro

TL;DR: Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro, but did not affect their viability, proliferation, motility, and ability to support synapses.
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THE GLUTAMINERGIC, GABAergic, DOPAMINERGIC BUT NOT CHOLINERGIC NEURONS ARE SUSCEPTIBLE TO ANAESTHESIA-INDUCED CELL DEATH IN THE RAT DEVELOPING BRAIN

TL;DR: It is suggested that anaesthetic exposure significantly increases neuroapoptosis of glutamatergic, GABAergic and dopaminergic neurons in the developing brain but not that of the cholinergic neuron in the basal forebrain.
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