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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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Citations
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MicroPET/CT Assessment of Minocycline Effects on Anesthetic-Induced Neuronal Injury in Developing Rats

TL;DR: It has been reported that blockade of NMDA receptors by ketamine may cause neurotoxicity in neonatal rats when given over a 12 hour period during the brain growth spurt.
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Depth of anaesthesia and mortality after cardiac or noncardiac surgery: a systematic review and meta-analysis of randomised controlled trials.

TL;DR: In this article , the authors performed a meta-analysis of mortality data from randomised trials of pEEG monitoring to assess the evidence of any protective effect of PEEG-guided light anaesthesia compared with deep anaesthesia in adults aged ≥18 yr.
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Neurocognitive and Quality-of-life Outcomes Following Intensive Care Admission: A Prospective 6-month Follow-up Study.

TL;DR: Patients discharged from the intensive care unit are at high risk for persistent cognitive impairment and poor quality of life score and there is an urgent need to prevent, diagnose, and manage these patients by optimizing intensive care practices.
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Anaesthesia and the developing nervous system: advice for clinicians and families

TL;DR: The concerns and the key recent literature are summarized and balanced advice is provided to clinicians to assist them in practice and in their discussions with families to ensure risks and benefits of anaesthesia in early life are explained.
References
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Journal ArticleDOI

The classical complement cascade mediates CNS synapse elimination.

TL;DR: It is shown that C1q, the initiating protein in the classical complement cascade, is expressed by postnatal neurons in response to immature astrocytes and is localized to synapses throughout the postnatal CNS and retina, supporting a model in which unwanted synapses are tagged by complement for elimination and suggesting that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease.
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Comparative aspects of the brain growth spurt

TL;DR: The brain in all species appears to grow through a sigmoid trajectory when its weight is plotted against its age, but the timing of the brain growth spurt is different in relation to birth in different species, so this must be one of the major factors to be taken into account when any attempt is made to extrapolate results obtained in one species to any other.
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Excitatory actions of gaba during development: the nature of the nurture.

TL;DR: This work proposes that GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions, and provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation.
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Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model

TL;DR: Reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Aβ levels, and protected both transgenic and nontransgenic mice against excitotoxicity.
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