Defining the role of NMDA receptors in anesthesia: Are we there yet?

Petrenko, Andrey B.; Yamakura, Tomohiro; Sakimura, Kenji; Baba, Hiroshi

doi:10.1016/j.ejphar.2013.11.039

Cited by 82 publications

(59 citation statements)

References 118 publications

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“…The exact mechanisms underlying actions of general anesthetics are still unclear. General anesthetics produce widespread depression in the CNS mainly by enhancing inhibitory neurotransmission and reducing excitatory neurotransmission (Garcia et al, 2010;Nelson et al, 2002;Petrenko et al, 2014). Volatile anesthetics including isoflurane and sevoflurane are widely used general anesthetics and interact with multiple molecular targets (Franks, 2008;Hemmings et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The General Anesthetic Isoflurane Bilaterally Modulates Neuronal Excitability

Zhao

Liu

et al. 2020

iScience

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Volatile anesthetics induce hyperactivity during induction while producing anesthesia at higher concentrations. They also bidirectionally modulate many neuronal functions. However, the neuronal mechanism is unclear. The effects of isoflurane on sodium channel currents were analyzed in acute mouse brain slices, including sodium leak (NALCN) currents and voltage-gated sodium channels (Na v) currents. Isoflurane at sub-anesthetic concentrations increased the spontaneous firing rate of CA3 pyramidal neurons, whereas anesthetic concentrations of isoflurane decreased the firing rate. Isoflurane at sub-anesthetic concentrations enhanced NALCN conductance but minimally inhibited Na v currents. Isoflurane at anesthetic concentrations depressed Na v currents and action potential amplitudes. Isoflurane at sub-anesthetic concentrations depolarized resting membrane potential (RMP) of neurons, whereas hyperpolarized the RMP at anesthetic concentrations. Isoflurane at low concentrations induced hyperactivity in vivo, which was diminished in NALCN knockdown mice. In conclusion, enhancement of NALCN by isoflurane contributes to its bidirectional modulation of neuronal excitability and the hyperactivity during induction.

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Section: Discussionmentioning

confidence: 99%

The General Anesthetic Isoflurane Bilaterally Modulates Neuronal Excitability

Zhao

Liu

et al. 2020

iScience

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“…Similarly, these two signals are vital to desflurane's effect on motor neurons (Figures and ). Moreover, the GABA and NMDA receptors are involved in desflurane's effect on neurons, these two receptors and related signals are targets for ongoing study to disclose the molecular mechanism underlying the neurotoxic effect of desflurane on motor neurons.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine prevents desflurane‐induced motor neuron death through NF‐KappaB pathway

Liu

Zhou

Wang

et al. 2019

Cell Biochemistry & Function

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Desflurane is one of the commonly used general anaesthetics. Recently, it was reported that desflurane caused neurotoxicity, raising concerns in clinical use. In this study, we found desflurane could affect viability and maturation in motor neurons.Dexmedetomidine, a α2-adrenergic receptor agonist, could attenuate the effect of desflurane on motor neurons. This process was mediated by NF-KappaB signalling.Interestingly, we also found that dexmedetomidine could recover the lesion in motor function and memory impaired by desflurane. Collectively, our results showed the neurotoxic effect of desflurane in motor neurons. More importantly, this process was alleviated by dexmedetomidine, potentially showing its application in protecting motor neuron from neurotoxic agents.Significance of the study: This work provides the evidence to support the protective role of dexmedetomidine in desflurane-induced motor neuron death. Since desflurane is a widely used anaesthetic in surgery and leads to neuron death, the neuroprotective effect of dexmedetomidine holds promising clinical application.

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“…Parenterally administered (e.g., etomidate, propofol, urethane, alpha-chloralose, ketamine, pentobarbital) and inhaled (e.g., halothane, enflurane, isoflurane, sevoflurane, desflurane, nitrous oxide) anesthetics significantly reduce neuronal action potential discharge frequency, manifesting as reductions of firing rate and spectral power of neural activity in peripheral neurograms and single-unit recordings (Sapru and Krieger, 1979). Mechanisms underlying the suppressive effects of anesthetics include potentiation of GABAergic signaling, suppression of N-methyl-D-aspartate (NMDA)-and non-N-methyl-D-aspartatedependent glutamatergic signaling, antagonism of neurolemmal membrane calcium ion channels, and modifications of neural plasmalemmal membrane fluidity (Kotani and Akaike, 2013;Petrenko et al, 2014). On a network level, anesthetics reduces the oscillatory synchrony between and amongst the sympathetic oscillators and the respiratory central pattern generator, thus compromising the principal neural output of studies seeking to interrogate mechanisms contributing to the regulation of arterial pressure and heart rate and generation of the breathing rhythm (Sapru and Krieger, 1979).…”

Section: Introductionmentioning

confidence: 99%

Microneurosurgical techniques and perioperative strategies utilized to optimize experimental supracollicular decerebration in rats

Ghali

2020

Journal of Integrative Neuroscience

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Defining the role of NMDA receptors in anesthesia: Are we there yet?

Cited by 82 publications

References 118 publications

The General Anesthetic Isoflurane Bilaterally Modulates Neuronal Excitability

The General Anesthetic Isoflurane Bilaterally Modulates Neuronal Excitability

Dexmedetomidine prevents desflurane‐induced motor neuron death through NF‐KappaB pathway

Microneurosurgical techniques and perioperative strategies utilized to optimize experimental supracollicular decerebration in rats

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