Dexmedetomidine Mitigates Microglial Activation Associated with Postoperative Cognitive Dysfunction by Modulating the MicroRNA-103a-3p/VAMP1 Axis

Abstract

Surgery-induced microglial activation is critical in mediating postoperative cognitive dysfunction (POCD) in elderly patients, where the important protective effect of dexmedetomidine has been indicated. However, the mechanisms of action of dexmedetomidine during the neuroinflammatory response that underlies POCD remain largely unknown. We found that lipopolysaccharide (LPS) induced substantial inflammatory responses in primary and BV2 microglial cells. The screening of differentially expressed miRNAs revealed that miR-103a-3p was downregulated in these cell culture models. Overexpression of miR-103a-3p mimics and inhibitors suppressed and enhanced the release of inflammatory factors, respectively. VAMP1 expression was upregulated in LPS-treated primary and BV-2 microglial cells, and it was validated as a downstream target of miR-103-3p. VAMP1-knockdown significantly inhibited the LPS-induced inflammatory response. Dexmedetomidine treatment markedly inhibited LPS-induced inflammation and the expression of VAMP1, and miR-103a-3p expression reversed this inhibition. Moreover, dexmedetomidine mitigated microglial activation and the associated inflammatory response in a rat model of surgical trauma that mimicked POCD. In this model, dexmedetomidine reversed miR-103a-3p and VAMP1 expression; this effect was abolished by miR-103a-3p overexpression. Taken together, the data show that miR-103a-3p/VAMP1 is critical for surgery-induced microglial activation of POCD.

Dexmedetomidine alleviates hippocampal neuronal loss and cognitive decline in rats undergoing open surgery under sevoflurane anaesthesia by suppressing CCAAT/enhancer‐binding protein beta

“…Perioperative administration of Dex also significantly improves early postoperative cognitive function in children undergoing tonsillectomy (Peng et al, 2021). Studies have found that Dex injection during laparoscopic cholecystectomy reduces serum proinflammatory cytokines and the occurrence of POCD (Wu et al, 2022; Yu et al, 2022). Dex was shown to reduce the severity of neuroinflammation and neuronal apoptosis in animal models of systemic inflammatory response syndrome (SIRS) and surgical injury (Du et al, 2021; Wang et al, 2020).…”

Amelioratory Effect of Melatonin on Cognition Dysfunction Induced by Sevoflurane Anesthesia in Aged Mice

“…For the open field test, the mice were housed in an open square plywood box and painted with flat black enamel paint (overall measurements of 72 cm (length), 30 cm (height), and 72 cm (breadth)) ( 21 ). Artificial light and darkness conditions were used to simulate the day and night environment.…”