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.

Deconstructing delirium in the post anaesthesia care unit

“…Multiple studies have found early engagement of the pre-frontal cortex after surgery, as demonstrated by early return of abstraction (Abstract Matching test) and vigilance (Psychomotor Vigilance Test), leading them to believe that the pre-frontal cortex has an important role in arousal from anaesthesia ( Huels et al, 2021 ; Mashour et al, 2021 , 2022 ; Rokos et al, 2021 ). Our assessment of vigilance and disordered thinking revealed similar results, with majority of individuals performing successfully on the tasks.…”

Altered Behavioral Responses Show GABA Sensitivity in Muscleblind-Like 2-Deficient Mice: Implications for CNS Symptoms in Myotonic Dystrophy

“…Because of the complicated nature of anesthetic administration in the DM1 population ( Gupta, 2009 ), our findings in Mbnl2 KO mice using sevoflurane highlight a potential aspect of impaired recovery from anesthesia in DM1 due the involvement of GABA. Emergence and recovery from anesthesia is a very involved process necessitating activity of various brain structures ( Hemmings et al, 2019 ), such as the prefrontal cortex ( Herrera et al, 2016 ; Huels et al, 2021 ) where γ2 S subunits are abundantly expressed ( Miralles et al, 1994 ).…”

Brain areas modulation in consciousness during sevoflurane anesthesia

“…Behavioral experiments showed that inactivated prefrontal and parietal cortices in mice could reduce the time of LORR, but only animals with an inactivated prefrontal cortex showed prolonged RR recovery time. These discrepancies highlight the frontal and parietal cortices as two discrete functional units, which roles need further studying (Pal et al, 2016 ; Huels et al, 2021 ).…”