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Building on their known ability to influence sleep and arousal, Li and colleagues show that modulating the activity of glutamatergic pedunculopontine tegmental neurones also alters sevoflurane-induced hypnosis. This finding adds support for the shared sleep-anaesthesia circuit hypothesis. However, the expanding recognition of many neuronal clusters capable of modulating anaesthetic hypnosis raises the question of how disparate and anatomically distant sites ultimately interact to coordinate global changes in the state of the brain. Understanding how these individual sites work in concert to disrupt cognition and behaviour is the next challenge for anaesthetic mechanisms research.
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http://dx.doi.org/10.1016/j.bja.2023.11.002 | DOI Listing |
Br J Anaesth
June 2025
Chronobiology and Sleep Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Neuroscience of Unconsciousness and Reanimation Research Alliance, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Anesthesiology and Critica
Background: It is hypothesised that general anaesthetics co-opt the neural circuits regulating endogenous sleep and wakefulness to produce hypnosis. To further probe this association, we focused on the GABAergic neurones of the parafacial zone (PZ), a brainstem site capable of promoting non-rapid eye movement sleep.
Methods: To determine whether PZ neurones are activated by a hypnotic dose of anaesthetics, c-Fos immunohistochemistry was performed.
Br J Anaesth
February 2024
Department of Anaesthesiology and Critical Care, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Center for Neuroscience of Unconsciousness and Reanimation Research Alliance, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Mahoney Insti
Building on their known ability to influence sleep and arousal, Li and colleagues show that modulating the activity of glutamatergic pedunculopontine tegmental neurones also alters sevoflurane-induced hypnosis. This finding adds support for the shared sleep-anaesthesia circuit hypothesis. However, the expanding recognition of many neuronal clusters capable of modulating anaesthetic hypnosis raises the question of how disparate and anatomically distant sites ultimately interact to coordinate global changes in the state of the brain.
View Article and Find Full Text PDFClin Toxicol (Phila)
June 2022
Department of Anesthesiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Background: Lipid emulsion infusion is a first-line therapy against the toxicity of local anesthetics and is a potential treatment for other drug overdoses, especially for highly lipophilic drugs. Considering the lipophilic property of volatile anesthetics, we hypothesized that lipid emulsion could reverse general anesthesia.
Methods: Using adult rats, we tested the effect of lipid emulsion infusion on time to emergence after discontinuation of sevoflurane and isoflurane, and further evaluated restoration of righting reflex under continuous sevoflurane anesthesia.
Br J Anaesth
May 2021
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
Background: Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating therapy in a sevoflurane dose-sparing approach.
View Article and Find Full Text PDFJ Clin Pharm Ther
December 2020
Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, China.
What Is Known And Objective: Sevoflurane is the most widely used volatile anaesthetic in clinical practice. It exhibits a hypnotic (unconsciousness) effect and causes a loss of reaction to noxious stimuli (immobility). However, to date, the mechanism of action of sevoflurane is poorly understood.
View Article and Find Full Text PDF