Possible neurotoxicity of the anesthetic propofol: evidence for the inhibition of complex II of the respiratory chain in area CA3 of rat hippocampal slices

Archives of Toxicology
Nikolaus BerndtAgustin Liotta

Abstract

Propofol is the most frequently used intravenous anesthetic for induction and maintenance of anesthesia. Propofol acts first and formost as a GABAA-agonist, but effects on other neuronal receptors and voltage-gated ion channels have been described. Besides its direct effect on neurotransmission, propofol-dependent impairment of mitochondrial function in neurons has been suggested to be responsible for neurotoxicity and postoperative brain dysfunction. To clarify the potential neurotoxic effect in more detail, we investigated the effects of propofol on neuronal energy metabolism of hippocampal slices of the stratum pyramidale of area CA3 at different activity states. We combined oxygen-measurements, electrophysiology and flavin adenine dinucleotide (FAD)-imaging with computational modeling to uncover molecular targets in mitochondrial energy metabolism that are directly inhibited by propofol. We found that high concentrations of propofol (100 µM) significantly decrease population spikes, paired pulse ratio, the cerebral metabolic rate of oxygen consumption (CMRO2), frequency and power of gamma oscillations and increase FAD-oxidation. Model-based simulation of mitochondrial FAD redox state at inhibition of different respiratory c...Continue Reading

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Citations

Jun 5, 2020·International Journal of Molecular Sciences·Nikolaus BerndtAgustin Liotta
Jun 27, 2019·Journal of Neurophysiology·Fahad IqbalNaweed I Syed
Feb 17, 2021·Anesthesia and Analgesia·Vincent C HsiehPhilip G Morgan
Apr 27, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nikolaus BerndtAgustin Liotta

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Methods Mentioned

BETA
sedation

Software Mentioned

Spike2
SPSS
Origin
MATLAB

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