Electrical stimulation of the parabrachial nucleus induces reanimation from isoflurane general anesthesia

Muindi, Fanuel; Kenny, Jonathan D.; Taylor, Norman E.; Solt, Ken; Wilson, Matthew A.; Brown, Emery N.; Dort, Christa J. Van

doi:10.1016/j.bbr.2016.03.021

Cited by 51 publications

(62 citation statements)

References 22 publications

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“…To date, activation of several brain regions has been reported to directly induce RORR in animals undergoing constant anesthesia. Electrical stimulation of the parabrachial nucleus (PBN) and optogenetic activation of dopamine neurons in the ventral tegmental area (VTA) both induce reanimation from isoflurane anesthesia (Muindi et al, 2016;Taylor et al, 2016); in addition, stimulation of the prefrontal cholinergic system by reverse dialysis delivery of 5 mM carbachol induces wake-like behavior in constant sevoflurane-anesthetized rats (Pal et al, 2018). Unlike these neurons, which play a decisive role in general anesthesia, cholinergic neurons of the BF may contribute to general anesthesia only through regulatory functions.…”

Section: Discussionmentioning

confidence: 99%

Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia

et al. 2020

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Cholinergic neurons in the basal forebrain (BF) have long been considered to be the key neurons in the regulation of cortical and behavioral arousal, and cholinergic activation in the downstream region of the BF can arouse anesthetized rats. However, whether the activation of BF cholinergic neurons can induce behavior and electroencephalogram (EEG) recovery from anesthesia is unclear. In this study, based on a transgenic mouse line expressing ChAT-IRES-Cre, we applied a fiber photometry system combined with GCaMPs expression in the BF and found that both isoflurane and propofol inhibit the activity of BF cholinergic neurons, which is closely related to the consciousness transition. We further revealed that genetic lesion of BF cholinergic neurons was associated with a markedly increased potency of anesthetics, while designer receptor exclusively activated by designer drugs (DREADD)-activated BF cholinergic neurons was responsible for slower induction and faster recovery of anesthesia. We also documented a significant increase in δ power bands (1-4 Hz) and a decrease in β (12-25 Hz) power bands in BF cholinergic lesioned mice, while there was a clearly noticeable decline in EEG δ power of activated BF cholinergic neurons. Moreover, sensitivity to anesthetics was reduced after optical stimulation of BF cholinergic cells, yet it failed to restore wakelike behavior in constantly anesthetized mice. Our results indicate a functional role of BF cholinergic neurons in the regulation of general anesthesia. Inhibition of BF cholinergic neurons mediates the formation of unconsciousness induced by general anesthetics, and their activation promotes recovery from the anesthesia state.

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Section: Discussionmentioning

confidence: 99%

Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia

et al. 2020

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“…40–42 Although anesthesiologists have pharmacological tools to antagonize specific drugs acting at specific receptors (e.g., benzodiazepines), 43 only recently has research focused on reversing anesthetic effects by promoting arousal systems. 1–3,12,4–6,8 This has been typically accomplished by either pharmacological manipulation using catecholamine reuptake inhibitors, 3,12 dopamine agonists, 4 central nervous system stimulants, 13 and nicotine, 1,3,12,4,6 or by electrical stimulation of specific brain regions such as the ventral tegmental area 5 or parabrachial nucleus. 8 In many of these studies, resumption of righting response (as a surrogate for emergence) was restored while the animal was still exposed to general anesthetics and a direct arousal promoting effect was observed.…”

Section: Discussionmentioning

confidence: 99%

“…1–8 In terms of reversing anesthetic effects, manipulations of the thalamus, 1,2 the cholinergic system, 9 and the dopaminergic system 5 have predominated. Nicotine infused in central median thalamus has been shown to reverse the effects of sevoflurane, 1 while infusing an antibody to a voltage-gated potassium channel in the same region reverses both sevoflurane and desflurane anesthesia.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 Most recently, there has been a focus of dopaminergic modulation through the administration of methylphenidate, 3,12,13 dopamine agonists, 4 or direct electrical stimulation of the ventral tegmental area; 5 Solt and colleagues have demonstrated that these pharmacological and nonpharmacological interventions induce reanimation in animals exposed to continuous propofol or isoflurane. 8 In terms of accelerating recovery after anesthetic discontinuation, caffeine has been recently shown to reduce the time to emergence from both propofol and isoflurane. 14 …”

Section: Introductionmentioning

confidence: 99%

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Paradoxical Emergence

Hambrecht-Wiedbusch

Mashour

2017

Anesthesiology

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Background Promoting arousal by manipulating certain brain regions and/or neurotransmitters has been a recent research focus, with the goal of trying to improve recovery from general anesthesia. The current study tested the hypothesis that a single subanesthetic dose of ketamine during isoflurane anesthesia would increase cholinergic tone in the prefrontal cortex and accelerate recovery. Methods Adult male rats were implanted with electroencephalography electrodes (frontal, parietal, and occipital cortex) and a microdialysis guide cannula targeted for the prefrontal cortex. After establishing general anesthesia with isoflurane, animals were randomly assigned to receive a saline control or ketamine injection. When isoflurane was discontinued nearly 90 min after drug or saline administration, recovery from anesthesia was measured by experimenters and blinded observers. During the entire experiment, electrophysiologic signals were recorded and acetylcholine was quantified by high-performance liquid chromatography with electrochemical detection. Results A single dose of subanesthetic ketamine caused an initial 125% increase in burst suppression ratio (last isoflurane sample: 37.48 ± 24.11% vs. isoflurane after ketamine injection: 84.36 ± 8.95%; P < 0.0001), but also a significant 44% reduction in emergence time (saline: 877 ± 335 s vs. ketamine: 494 ± 108 s; P = 0.0005; n = 10 per treatment). Furthermore, ketamine caused a significant 317% increase in cortical acetylcholine release (mean after ketamine injection: 0.18 ± 0.16 pmol vs. ketamine recovery: 0.75 ± 0.41 pmol; P = 0.0002) after isoflurane anesthesia was discontinued. Conclusions Administration of subanesthetic doses of ketamine during isoflurane anesthesia increases anesthetic depth but—paradoxically—accelerates the recovery of consciousness, possibly through cholinergic mechanisms.

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“…Ambiguity in gamma frequency changes can occur during emergence from anesthesia 10,11 . The accepted view states that awakening in rodents correlates with individual events, such as spontaneous movement of a body part 12 , motor response after painful stimuli 8 or righting reflex 4,6,13 and implies that a single event can denote the restoration of motor behavior from a coma-like state. The righting reflex is considered the gold standard test to assess arousal in rodents, because vestibular inputs that sense head movement typically indicate awareness of the surroundings 2,14 .…”

Section: Introductionmentioning

confidence: 99%

Continuous regimens of cortico-motor integration calibrate levels of arousal during emergence from anesthesia

Gao

Calderon

2020

Preprint

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31Background: Recovery to a conscious state when emerging from anesthesia requires 32 full cortical desynchronization, initiation of movement and behavioral reactivity to 33 sensory stimuli. However, the variety of cortical electroencephalogram (EEG) patterns 34 associated with specific anesthetics and the paucity of behavioral descriptions during 35 emergence from anesthesia have prevented EEG and behavior as feasible tracking 36 methods to assess emerging from anesthesia. We propose a detailed combined 37 analysis of motor and cortical activity to determine levels of arousal in rodents. 39Methods: Using decreasing anesthetic concentrations, we simultaneously recorded 40 local field potentials (LFPs) and movement in mice. We delineated cortical dynamics 41 and sub-states during emergence from anesthesia by applying a smoothed-Z score to 42 extract dominant frequencies from spectrogram. Then, we implemented KMeans to 43 obtain cortical sub-states. Finally, we used density estimation and an abrupt change 44 detection algorithm to segment cortical activity into periods. We used cortical sub-states 45 obtained during isoflurane traces to supervise sub-states in sevoflurane and a 46 pharmacologically induced-arousal model. This information together with examining 47 videos were used to categorize behavior. 49Results: We identified five cortical periods with restored motor behavior during 50 emergence from isoflurane anesthetic. Periods of structured sub-states denoted when 51 specific motor behaviors occurred. No significant differences were found when 52 comparing the combined cortical features and motor behavior using isoflurane, 53 3 sevoflurane and our arousal-rodent model. We describe graded regimens of cortico-54 motor activity during emergence from anesthesia to assess arousal levels. 55 56 Conclusion: We show cortical patterns denote gradual motor behaviors when emerging 57 from anesthesia. Restoring motor behavior is a dynamic process that begins tens of 58 minutes earlier than the righting reflex. Combining cortical activity and motor behavior 59 unveils novel biomarkers to accurately track emerging from general anesthesia in 60 rodents and likely other species. 61 62 Key words: Emergence from anesthesia, movement, behavioral arousal, cortical 63 biomarkers, cortical periods, spectral analysis, smoothed Z score algorithm, k-means 64 classifier, righting reflex 65 66 67 68 69 70 71 72 4Introduction: 73 Recovery to a conscious state in humans usually comprises full cortical 74 desynchronization, initiation of movement and behavioral reactivity to sensory stimuli 1 . 75 However, the combination of these parameters in rodents is rarely used when assessing 76 arousal when emerging from anesthesia 2 or when investigating the neuronal pathways 77 underlying reversing anesthetic states in animal models 3-6 . A clear discrepancy arises 78 when analyzing cortical activity 7 and behavior among anesthetics. Some data suggests 79 excluding these parameters. For example, the onset of movement during the emergence 8...

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Electrical stimulation of the parabrachial nucleus induces reanimation from isoflurane general anesthesia

Cited by 51 publications

References 22 publications

Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia

Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia

Paradoxical Emergence

Continuous regimens of cortico-motor integration calibrate levels of arousal during emergence from anesthesia

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