Press Release2022.2.22｜International Institute for Integrative Sleep Medicine (WPI‐IIIS)

Sevoflurane Improves Sleep Alteration in Responseto Inflammation
Researchers at the University of Tsukuba investigate the effect of thegeneral anesthetic sevoflurane on sleep disturbance caused by systemic
inflammation
Tsukuba, Japan – Getting a good night’s sleep can sometimes be achallenge, but inflammation may make it even more difficult. While therelationship between inflammation and sleep alteration has beenpreviously shown, researchers in Japan have now identified a potential
method to overcome sleep disturbance associated with systemic
inflammation.
In a new study published in Journal of sleep research , researchers at
the University of Tsukuba examined the effect of sevoflurane, an anesthetic
agent used to maintain unconsciousness during surgery, on sleep recovery
in a mouse model of systemic inflammation.
Systemic inflammation has been shown to affect sleep quality byreducing the amount of time spent in the rapid eye movement (REM) andwaking states and increasing the amount of time spent in the non-REM state.
Previous animal studies have illustrated the protective effects ofsevoflurane on organs, including the brain, but the relationship between
sevoflurane and sleep has not been explored under inflammatory
conditions. Using a model in which mice are injected with the endotoxin
lipopolysaccharide (LPS) to induce inflammation throughout the body, theresearch team evaluated the effects of sevoflurane on altered sleep
patterns associated with systemic inflammation.
“We hypothesized that preconditioning with sevoflurane prior toinducing inflammation by LPS would promote sleep recovery,” says mainauthor Professor Takashi Kanbayashi.
The research team exposed mice to sevoflurane prior to LPS injection(“preconditioning”) and also examined the effects of sevoflurane exposure
after LPS injection (“postconditioning”). Control mice without systemic
inflammation were exposed to either sevoflurane or air and received either
sterile saline or LPS injection. The researchers monitored the sleep patternsof the mice using electroencephalography and collected brain tissues forhistological analysis.
“We found that mice that were preconditioned with sevoflurane
showed a significant increase in REM sleep after LPS injection,” says
Professor Kanbayashi. “This effect was not observed in mice that receivedpostconditioning.”
Examination of brain tissues from mice treated with LPS alone
revealed a reduction in neurons expressing the neuronal activation marker
Fos in the pedunculopontine tegmental nucleus and laterodorsal tegmental
nucleus (PPTg/LDTg), which is an area of the brain involved in the regulationof REM sleep. However, the mice that received sevoflurane preconditioning
before LPS treatment maintained similar levels of Fos-positive neurons as
those observed in the control mice. These results demonstrate thatmaintained activation of neurons in the PPTg/LDTg region may represent apotential mechanism underlying the effect of sevoflurane on sleep
reintegration under inflammatory conditions.
The findings of this study indicate a potential application for
sevoflurane in the treatment of sleep disturbance associated with systemic
inflammation.
The article, “Effect of sevoflurane preconditioning on sleep
reintegration after alteration by lipopolysaccharide,” was published in
Journal of sleep research at DOI: 10.1111/jsr.13556.
This work was supported by a JSPS KAKENHI Grant-in-Aid (C) [grantnumbers 19K07314 to YIT and 19 K08037 to TK]; The Japan Agency for
Medical Research and Development [grant number JP20dm0107162] to TK;
a Grant-in-Aid for Scientific Research on Innovative Areas, ‘Willdynamics’[grant number 17H06049] to YIT; a grant from the World PremierInternational Research Centre Initiative (WPI), Japan, IIIS; the Ministry ofEducation, Culture, Sports, Science and Technology World Premier Japan
Society for the Promotion of Science KAKENHI [grant number 17H06095];
the International Research Centre Initiative, CREST [grant numberA3A28043]; the Funding Program for World-Leading Innovative R&D on
Science and Technology from JSPS; the Uehara Memorial Foundation
research grant; and a Takeda Science Foundation research grant to MY. The
study sponsors had no role in the study design, collection, analysis, orinterpretation of data, writing the report, or the decision to submit thereport for publication.

Fig1. Sevoflurane preconditioning promotes sleep recovery from lipopolysaccharide alteredsleep

Fig2. The time spent in REM and waking states increases with sevoflurane preconditioning.

Bibliographic information
Nemoto T, Irukayama-Tomobe Y, Hirose Y, Tanaka H, Takahashi G, TakahashiS,
Yanagisawa M, Kanbayashi T. (2022) Effect of sevoflurane preconditioning on sleep
reintegration after alteration by lipopolysaccharide.
Journal of Sleep Research, e13556
doi: 10.1111/jsr.13556
Media Contact
Alliance and Communication Unit, International Institute for Integrative Sleep Medicine(WPI-IIIS), University of Tsukuba, Japan
E-mail: wpi-iiis-alliance@ml.cc.tsukuba.ac.jp