Introduction Remimazolam is a novel benzodiazepine γ-aminobutyric acid A (GABAa) receptor agonist used for sedation and the induction as well as maintenance of general anesthesia. Previous research proved that anesthetic agents acting on GABAa receptor, such as thiopentone, propofol and midazolam, have protective actions for cerebral ischemia/reperfusion (I/R) injury. We here probed into remimazolam for its protective effect and potential mechanism of action against cerebral I/R injury. Material and Methods A rat model of middle cerebral artery occlusion (MCAO) with focal transient cerebral I/R injury was established and was given tail vein injection of gradient remimazolam (5, 10, 20 mg/kg) after 2 h of ischemia. Following 24 h of reperfusion, neurological function, brain infarct volume, morphology of cerebral cortical neurons, and expressions of corticocerebral NLRP3, ASC, caspase-1, GSDMD, IL-1β and IL-18 were evaluated. Results The results showed that remimazolam could effectively improve the neurological dysfunction, reduce the infarct volume and alleviate the damage of cortical neurons after I/R injury. Notably, the expression of NLRP3 inflammasome pathway was down-regulated, suggesting that remimazolam exerted protective actions on I/R injury by suppressing pyroptosis with decreased expression and release of inflammatory factors, and the involvement of the NLRP3 inflammasome pathway might be the core during that process. Overall, our results indicate that NLRP3 inflammation is a promising target. Conclusion Based on this mechanism, remimazolam may be one of the ideal anesthetic drugs for patients with ischemic stroke.

Background: Sleep deprivation (SD) causes a disturbance in the cognitive function of rats. While propofol has a powerful sedative and hypnotic effect and is an antioxidant, its effect on the cognitive function of rats following SD remains unknown. The purpose of this study was to explore the protective effects of propofol on excessive autophagy and mitophagy in the hippocampus of rats after SD.Methods: Adult male rats were intraperitoneally injected with 30 mg/kg of propofol after 96 hours of SD.Then we evaluated the effect of propofol on the cognitive function of sleep deprived rats by the Morris water maze. Transmission electron microscopy, Western blotting, PCR, immunohistochemistry, autophagy enhancer and autophagy inhibitor were used to study the effect of propofol on hippocampal neurons of rat with excessive autophagy and mitophagy. Results:The behavioral experimental results of the Morris water maze showed that propofol improved the learning and memory ability of sleep-deprived rats. The expression of Beclin1, PINK1, parkin, p62, and LC3 protein increased significantly after sleep deprivation. While the intervention of propofol could significantly reduce the expression of these proteins, rapamycin treatment eliminated this effect.Conclusions: Our findings showed that propofol could reduce the impairment of learning and memory in sleep-deprived rats by inhibiting excessive autophagy and mitophagy in hippocampal neurons. This strategy may provide an application basis for the clinical use of propofol in patients with chronic insomnia.

Objective This study was designed to evaluate the neurotoxicity of dexmedetomidine combined with ropivacaine for continuous femoral nerve block in rabbits. Methods Thirty New Zealand rabbits were randomly divided into 5 groups of 6 rabbits each and received a continuous femoral nerve block with saline; 0.25% ropivacaine; or 1, 2, or 3 µg/mL of dexmedetomidine added to 0.25% ropivacaine (Groups A–E, respectively). Sensory and motor function was assessed after the nerve block. The rabbits were anesthetized and killed after 48 hours of a continuous femoral nerve block, and the femoral nerves were removed for light and electron microscopy analyses. Results The behavior scores were highest in Group A at 2 and 6 hours after injection. The scores were higher in Groups B and C than in Groups D and E at these same time points. All groups showed normal pathological tissues in the femoral nerves under optical microscopy. Under electron microscopy, histological abnormalities were observed only in Group E; none of the other groups exhibited pathological abnormalities. Quantitative analysis of the myelin sheath area revealed no significant difference in the axonal area, total area of the myelin sheath, or ratio of the total axonal area to the total area of the myelin sheath in all groups. Conclusion The lowest doses of dexmedetomidine (1 and 2 µg/mL) combined with 0.25% ropivacaine for continuous femoral nerve block resulted in no neurotoxic lesions, but the higher dose (3 µg/mL) resulted in neurotoxic lesions in this rabbit experimental model.

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