Systemic inflammation might be connected to the cognitive impairment reported in patients with sepsis or after major surgery. Dexmedetomidine (DEX), a drug that acts as an agonist of α2-adrenergic receptors, has been hypothesized to be neuroprotective, with reports showing that DEX reduces neuroinflammation in lipopolysaccharide (LPS) mouse models. Previous work has shown that DEX enhances the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2), a regulatory factor of cellular antioxidant defense involved in the regulation of stress and neuroinflammation. However, the role of Nrf2 in cognitive impairment remains unknown. A study in Behavioral Brain Research studied the effects of knocking out Nrf2 on DEX’s neuroprotective effect. First, the team confirmed that DEX administration improved LPS-induced cognitive dysfunction in mice, reducing microglial activation and the production of pro-inflammatory cytokines. DEX also activated the Nrf2 signaling pathway in the hippocampus, upregulating antioxidant enzymes. Knocking out Nrf2 reversed the beneficial effects of DEX on cognitive impairment in the LPS mouse model. These results shed light on the neuroprotective mechanisms of DEX and the role of Nrf2 in this process.

Original reference: Chen, L. et al. Behav. Brain Res. 469,115006 (2024)

全身炎症可能与脓毒症患者或大手术后的认知障碍有关。右美托咪定 (DEX) 是一种充当 α2-肾上腺素能受体激动剂的药物，据推测具有神经保护作用，有报告显示，DEX 可减少脂多糖 (LPS) 小鼠模型中的神经炎症。先前的研究表明，DEX 增强核因子红细胞 2 相关因子 2 (Nrf2) 的表达，Nrf2 是细胞抗氧化防御的调节因子，参与应激和神经炎症的调节。然而，Nrf2 在认知障碍中的作用仍不清楚。行为大脑研究中的一项研究研究了敲除Nrf2对 DEX 神经保护作用的影响。首先，研究小组证实 DEX 给药改善了 LPS 诱导的小鼠认知功能障碍，减少了小胶质细胞的激活和促炎细胞因子的产生。 DEX 还激活海马体中的 Nrf2 信号通路，上调抗氧化酶。在 LPS 小鼠模型中，敲除Nrf2可以逆转 DEX 对认知障碍的有益影响。这些结果揭示了 DEX 的神经保护机制以及 Nrf2 在此过程中的作用。

原始参考： Chen, L. et al.行为。脑研究。 469,115006 (2024)