Dexmedetomidine mitigates neuroinflammation and improves early postoperative neurocognitive dysfunction in rats by enhancing autophagy

Abstract

Postoperative neurocognitive dysfunction (PND) is a common postoperative complication. Autophagy is correlated with the pathogenesis of PND. This study investigated the potential role of autophagy in the neuroprotection of Dexmedetomidine (Dex) pretreatment in PND. The PND rat model was established by abdominal surgery. The cognitive function of rats was evaluated by Y-maze 3 days after surgery. Nissl staining assessed postoperative hippocampal damage. Immunofluorescence detected the expression of microglial activation (Iba-1) and autophagy-related protein (LC3B) in hippocampal tissues. Western blot detected the autophagy-related protein expression (Beclin 1, LC3B, and p62), proinflammatory cytokines, and the protein activation of the LKB1/AMPK/ULK-1 signaling pathway. RT-PCR quantified the expression of IL-1β, TNF-α, and IL6. In this study, we found Dex pretreatment improved spatial memory function impairment and reduced abdominal surgery-induced hippocampal tissue damage. Dex pretreatment significantly increased the expression of Beclin 1 and LC3 II/I, and decreased the expression of p62 in the hippocampus after surgery. Furthermore, Dex effectively inhibited microglial activation and proinflammatory cytokines by enhancing autophagy in the hippocampus. Pretreatment with 3-MA, an autophagy inhibitor, the inhibitory effect of Dex on postoperative neuroinflammation was significantly weakened. We further demonstrated that Dex suppressed surgery-induced neuroinflammation by activating the LKB/AMPK/ULK1 signaling pathway. In conclusion, our study indicated that Dex inhibited hippocampal neuroinflammation and ameliorated PND by enhancing autophagy after surgery in rats, which was related to the LKB1/AMPK/ULK1 signaling pathway. These findings provide a potential therapeutic prospect for PND.

Taming Postoperative Delirium with Dexmedetomidine: A Review of the Therapeutic Agent’s Neuroprotective Effects following Surgery

“…Rats were divided into pre-treatment with either dexmedetomidine or saline before surgery. In the dexmedetomidine pre-treatment group, there was a significant decrease in inflammatory markers, including IL-6 [58]. When the dexmedetomidine pretreated group was exposed to yohimbine, an alpha 2 -adrenergic receptor antagonist, there was no significant change compared to the saline pre-treatment group, implying that this reduction in inflammatory markers is mediated by the alpha 2 -adrenergic receptor agonism of dexmedetomidine.…”

“…Again, there was visibly reduced nerve cell loss on hippocampal tissue sampling when they were pre-treated with dexmedetomidine [58]. This group of investigators had two groups pre-treated with dexmedetomidine, one that was exposed to 3-methyladenine, an autophagy inhibitor, and another that was able to undergo autophagy.…”