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Inactivation of Prefrontal Cortex Delays Emergence From Sevoflurane Anesthesia.

ABSTRACT: Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex-somatosensory barrel field and medial/lateral parietal association cortex-would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.

SUBMITTER: Huels ER

PROVIDER: S-EPMC8299111 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCholinergic stimulation of prefrontal cortex (PFC) can reverse anesthesia. Conversely, inactivation of PFC can delay emergence from anesthesia. PFC receives cholinergic projections from basal forebrain, which contains wake-promoting neurons. However, the role of basal forebrain cholinergic neurons in arousal from the anesthetized state requires refinement, and it is currently unknown whether the arousal-promoting effect of basal forebrain is mediated through PFC. To address these gaps in knowledge, we implemented a novel approach to the use of chemogenetic stimulation and tested the role of basal forebrain cholinergic neurons in behavioral arousal during sevoflurane anesthesia. Next, we investigated the effect of tetrodotoxin-mediated inactivation of PFC on behavioral arousal produced by electrical stimulation of basal forebrain during sevoflurane anesthesia.MethodsAdult male and female transgenic rats (Long-Evans-Tg [ChAT-Cre]5.1 Deis; n = 22) were surgically prepared for expression of excitatory hM3D(Gq) receptors or mCherry in basal forebrain cholinergic neurons, and activation of these neurons by local delivery of compound 21, an agonist for hM3D(Gq) receptors. The transgenic rats were fitted with microdialysis probes for agonist delivery into basal forebrain and simultaneous prefrontal acetylcholine measurement. Adult male and female Sprague Dawley rats were surgically prepared for bilateral electrical stimulation of basal forebrain and tetrodotoxin infusion (156 μM and 500 nL) into PFC (n = 9) or bilateral electrical stimulation of piriform cortex (n = 9) as an anatomical control. All rats were implanted with electrodes to monitor the electroencephalogram. Heart and respiration rates were monitored using noninvasive sensors. A 6-point scale was used to score behavioral arousal (0 = no arousal and 5 = return of righting reflex).ResultsCompound 21 delivery into basal forebrain of rats with hM3D(Gq) receptors during sevoflurane anesthesia produced increases in arousal score (P < .001; confidence interval [CI], 1.80-4.35), heart rate (P < .001; CI, 36.19-85.32), respiration rate (P < .001; CI, 22.81-58.78), theta/delta ratio (P = .008; CI, 0.028-0.16), and prefrontal acetylcholine (P < .001; CI, 1.73-7.46). Electrical stimulation of basal forebrain also produced increases in arousal score (P < .001; CI, 1.85-4.08), heart rate (P = .018; CI, 9.38-98.04), respiration rate (P < .001; CI, 24.15-53.82), and theta/delta ratio (P = .020; CI, 0.019-0.22), which were attenuated by tetrodotoxin-mediated inactivation of PFC.ConclusionsThis study validates the role of basal forebrain cholinergic neurons in behavioral arousal and demonstrates that the arousal-promoting effects of basal forebrain are mediated in part through PFC.

Project description:Children with cerebral palsy can demonstrate irritability following emergence from general anaesthesia. As well, an elevated rate of emergence delirium (ED) in children has been associated with the application of sevoflurane. The current study's intent is to administer dexmedetomidine, in a single dosage administration, at the initial phase of sevoflurane based anesthesia with regard to the occurrence and severity of ED in children afflicted with cerebral palsy. Participating in the study (American Society of Anesthesiologists I-II) are eighty children ranging in ages two through twelve years. They would be anaesthetised with sevoflurane based anesthesia while undergoing lower limb surgical procedures. The participants were equally distributed to either Group c or Group D. Group C was administered 10 ml saline 0.9%, and Group D was administered dexmedetomidine 0.5 μg•kg(-1). Five minutes prior to commencement of the surgical procedures, the participants received the prescribed pharmaceutical dosages under the anesthesia of sevoflurane. In order to sustain the BIS values in a range of 45 and 55, at 60 second increments, endtidal sevoflurane concentrations (ETsev) were modified. After conclusion of the surgical procedures, in post anesthesia care unit (PACU), the frequency of ED was gauged with Aonos four point scale and the severity of ED was gauged with pediatric anesthesia emergence delirium scale upon admission (T0), after intervals of five minutes (T5), fifteen minutes (T15) and thirty minutes (T30). Extubation time, emergence time and length of at stay at the PACU were assessed. Relative to Group C, participants of Group D exhibited noticeably shortened times of emergence, extubation and PACU duration of stay. Prior to surgical incision, ETsev was elevated in the control group, (1.9±0.2 vs 1.6±0.3; P = 0.023) and amid the initial 20 minutes following the surgical incision (1.6±0.2 vs 1.1±0.2; P = 0.016). At intervals of commencement, T0, of five minutes (T5) and fifteen minutes T15, Group D exhibited lower occurrences and severity of ED than those participants in Group C. Dexmedetomidine, given as a bolus dose post induction, was effective in reducing the occurrence and severity of emergence delirium in children with cerebral palsy who were undergoing lower limb surgical procedures under sevoflurane anaesthesia.

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Inactivation of Prefrontal Cortex Delays Emergence From Sevoflurane Anesthesia.

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