Background: Surgery and anesthesia-induced perioperative neurocognitive disorder (PND) are closely related to NOD-like receptors (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome microglia inflammatory response. Inhibiting the occurrence of neuroinflammation is an important treatment method to improve postoperative delirium. Fewer NLRP3-targeting molecules are currently available in the clinic to reduce the incidence of postoperative delirium. Dexmedetomidine (DEX), an α2 adrenergic receptor agonist has been shown to have antioxidant and anti-inflammatory activities. The present study showed that DEX reduced the production of cleaved caspase1 (CASP1) and destroyed the NLRP3–PYD And CARD Domain Containing (PYCARD)–CASP1 complex assembly, thereby reducing the secretion of IL-1β interleukin beta (IL-1β). DEX promoted the autophagy process of microglia and reduced NLRP3 expression. More interestingly, it promoted the ubiquitination and degradation of NLRP3. Thus, this study demonstrated that DEX reduced NLRP3-mediated inflammation through the activation of the ubiquitin-autophagy pathway. This study provided a new mechanism for treating PND using DEX.Methods: C57BL/6 mice were pre-administered DEX 3 days in advance, and an abdominal exploration model was used to establish a perioperative neurocognitive disorder model. The anti-inflammatory effect of DEX was explored in vivo by detecting NLRP3-CASP1/IL-1β protein expression and behavioral testing. Primary microglia were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in vitro, the expression of CASP1 and IL-1β was detected in the supernatant of cells, and the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) and sequestosome 1 (SQSTM1) was examined in the cytoplasm. Meanwhile, Co-immunoprecipitation (Co-IP) was used to detect NLRP3 protein ubiquitination so as to clarify the new mechanism underlying the anti-inflammatory effect of DEX.Results: Pre-administration of DEX reduced the protein expression of NLRP3, CASP1, and IL-1β in the hippocampus of mice induced by surgery and also improved the impairment of learning and memory ability. At the same time, DEX also effectively relieved the decrease in spine density of the hippocampal brain induced by surgery. DEX decreased the cleaved CASP1 expression, blocked the assembly of NLRP3–PYCARD–CASP1 complex, and also reduced the secretion of mature IL-1β in vitro. Mechanically, it accelerated the degradation of NLRP3 inflammasome via the autophagy–ubiquitin pathway and reduced the green fluorescent protein/red fluorescent protein MAP1LC3B ratio, which was comparable to the effect when using the autophagy activator rapamycin (Rapa). Furthermore, it increased the ubiquitination of NLRP3 after LPS plus ATP stimulated microglia.Conclusion: DEX attenuated the hippocampal brain inflammation by promoting NLRP3 inflammasome degradation via the autophagy–ubiquitin pathway, thus improving cognitive impairment in mice.

Sevoflurane is one of the most commonly used inhaled anesthetics due to its low blood gas coefficient, fast onset, low airway irritation, and aromatic smell. However, recent studies have reported that sevoflurane exposure may have deleterious effects on cognitive function. Although neuroinflammation was most widely mentioned among the established mechanisms of sevoflurane-induced cognitive dysfunction, its upstream mechanisms have yet to be illustrated. Thus, we reviewed the relevant literature and discussed the most mentioned mechanisms, including the modulation of the microglial function, blood–brain barrier (BBB) breakdown, changes in gut microbiota, and ease of cholinergic neurotransmission to help us understand the properties of sevoflurane, providing us new perspectives for the prevention of sevoflurane-induced cognitive impairment.

Fulminant myocarditis (FM) is a severe disease with a rapidly progressive and life-threatening course caused mainly by viral infection. The symptoms, laboratory findings, and presence of ECG changes resemble acute coronary syndrome. Therefore, coronary angiography is usually helpful in making the appropriate diagnosis. However, failure to obtain complete coronary artery images due to coronary artery anatomic variations poses a challenge for the diagnosis of FM. Here, we report a case of FM preliminarily diagnosed as acute coronary syndrome (ACS) due to the presence of coronary artery anomaly.