Effect of sevoflurane preconditioning on sleep reintegration after alteration by lipopolysaccharide

Tsuyoshi Nemoto, Yoko Irukayama-Tomobe, Yuki Hirose, Hiromu Tanaka, Genki Takahashi, Satoshi Takahashi, Masashi Yanagisawa, Takashi Kanbayashi

Research output: Contribution to journalArticlepeer-review


Despite extensive evidence on the organ protective effects of sevoflurane, its effect on disturbed sleep remains unclear. We hypothesised that sevoflurane preconditioning positively impacts disturbed sleep caused by systemic inflammation. A prospective, randomised laboratory investigation was conducted in C57BL/6J mice. A mouse model of lipopolysaccharide (LPS)-induced systemic inflammation was employed to investigate the effects of sevoflurane on sleep recovery. Symptom recovery was evaluated through electroencephalography/electromyography (EEG/EMG) and histological studies. The mice were exposed to 2% sevoflurane before and after peritoneal injection of LPS. The EEG and EMG were recorded for 24 h after the procedure. Brain tissue was harvested after the sevoflurane/LPS procedure and was immunostained using individual antibodies against choline acetyltransferase (ChAT) and Fos. The ChAT-positive and ChAT/Fos double-positive cells were analysed quantitatively in the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus (PPTg/LDTg). Compared with control mice, mice preconditioned with sevoflurane but not post-conditioned showed a significant increase in rapid eye movement (REM) sleep during EEG recording following the LPS challenge. They also demonstrated a shorter REM latency, indicating an early recovery from LPS-altered sleep. The bouts of REM episodes were retained with sevoflurane preconditioning. More ChAT/Fos double-positive cells were observed in the PPTg/LDTg in the sevoflurane preconditioning plus LPS group than in the LPS-only group. Sevoflurane preconditioning promotes recovery from altered sleep induced by systemic inflammation. Activation of PPTg/LDTg is considered a mechanism underlying sleep reintegration. The recovery phenomenon shows potential for clinical application in cases of sleep disturbances induced by systemic inflammation.

Original languageEnglish (US)
JournalJournal of Sleep Research
StateAccepted/In press - 2022
Externally publishedYes


  • electroencephalography
  • pedunculopontine tegmental nucleus/laterodorsal tegmental nucleus
  • sevoflurane
  • sleep
  • systemic inflammation

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Behavioral Neuroscience


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