Sevoflurane attenuates cognitive dysfunction and NLRP3-dependent caspase-1/11-GSDMD pathway-mediated pyroptosis in the hippocampus via upregulation of SIRT1 in a sepsis model.

Abstract:

:Septic encephalopathy (SE) is a devastating consequence of sepsis, a hyper-triggered host response against infectious challenge, which ultimately leads to brain damage. The present study examined whether sevoflurane (SVF), a volatile anaesthetic, can counteract the perturbation of homeostasis in a caecal ligation and puncture (CLP)-induced mouse model of SE. SVF enhances neurocognition in terms of spatial memory improvement via counter-regulation of activated oxidative-inflammatory stress and pyroptotic processes in SE. Further, the beneficial effects of SVF against SE are mediated by activation of silent information regulator 1 (SIRT1)-mediated reduction of reactive oxygen species (ROS) level, regulation of thioredoxin (TXN) and thioredoxin interacting protein (TIP) levels, reduction of inflammatory-pyroptotic signalling (NLRP3, caspase 1/11, GSDMD, TLR4 and TRIF) proteins, as well as a reduction of inflammatory cytokine (IL-1β and IL-18) levels. These findings suggest that SVF may have therapeutic potential for the treatment of SE and associated cognitive malfunction.

journal_name

Arch Physiol Biochem

authors

Chen H,Peng Y,Wang L,Wang X

doi

10.1080/13813455.2020.1773860

subject

Has Abstract

pub_date

2020-06-13 00:00:00

pages

1-8

eissn

1381-3455

issn

1744-4160

pub_type

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