Abstract
Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of sevoflurane. We found that sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
Highlights
Sevoflurane, a commonly used anesthetic, may cause agitation in patients
We found that the administration of 2% sevoflurane induced a behavioral hyperactivity in postnatal 10 (P10) mice at the first minute after the loss of righting reflex, which was about two minutes after the sevoflurane administration (Fig. 1b and the video in Supplemental Data), with 60% of mice (n = 10) exhibiting hyperactivity (Fig. 1c; χ2 = 5.952, P = 0.015)
We found that inhalational anesthetic sevoflurane was able to increase neuronal activation in somatosensory cortex of young mice (P10) within one minute after the administration of sevoflurane, and to induce behavioral hyperactivity at one minute after the loss of righting reflex, which was about two minutes after the administration of sevoflurane
Summary
Sevoflurane, a commonly used anesthetic, may cause agitation in patients. the mechanism underlying this clinical observation remains largely unknown. The outcomes of the study would demonstrate that inhalational anesthetics may induce increases in neuronal activation and behavioral hyperactivity in mice, and will establish a system to determine the underlying mechanism by which patients develop agitation in the induction of general anesthesia or emergence from general anesthesia. Ton and colleagues showed an increase of locomotor activity in mice during the induction of sevoflurane anesthesia and this increase in locomotor activity lasted for five minutes after the recovery from the sevoflurane[11] These studies did not assess the neuronal activity of the mice at the time when they exhibited hyperactive behavior. The neuronal mechanisms underlying the anesthesia-associated behavioral hyperactivity remain unknown
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