Dexmedetomidine attenuates LPS‐mediated BV2 microglia cells inflammation via inhibition of glycolysis

Abstract

Meng and Yu Equal contributes. A B S T R A C TMicroglia inflammation induces pro-inflammatory cytokines and pro-inflammatory enzymes expression, thus leading to inflammation-mediated neuronal cell death. Increased intracellular glycolysis participates in LPS-mediated microglia inflammation. Dexmedetomidine exhibits neuroprotective effects in some situations. In this study, we mainly focused on whether and how dexmedetomidine inhibits LPS-mediated cellular glycolysis and inflammation in BV2 cells. LPS induced pro-inflammatory cytokines and pro-inflammatory enzymes expression, and increased glycolysis capacity in BV2 cells. Moreover, inhibition of glycolysis by 2DG attenuated LPS-induced pro-inflammatory cytokines and pro-inflammatory enzymes expression. Moreover, LPS upregulated hypoxia-inducible factor 1a (HIF1a) expression and decreased sirt1 expression. Dexmedetomidine counteracted these effects induced by LPS. Further, 2-methoxyestradiol, a HIF1a inhibitor, could inhibit LPSmediated glycolysis and inflammation in BV2 cells, which was similar to the effects of dexmedetomidine. In addition, these effects of dexmedetomidine could be reversed by EX527, a sirt1 inhibitor. The present study indicated that dexmedetomidine, via upregulation of sirt1 expression, inhibited HIF-1a expression and glycolysis, thus reducing LPS-mediated inflammation in BV2 cells.

Dexmedetomidine Alleviates Inflammatory Response and Oxidative Stress Injury of Vascular Smooth Muscle Cell via α2AR/PI3K/AKT Pathway in Intracranial Aneurysm

“…During the rst 24 h after admission, low dosage DEX leads to favorable neurological outcomes in patients with SAH [39]. DEX alleviates the lipopolysaccharide-induced in ammation responses to microglia cells by suppressing glycolysis [40]. DEX alleviates hippocampal in ammation to protect aged rats against postoperative cognitive dysfunction [41].…”

Dexmedetomidine Alleviates Microglia-Induced Spinal Inflammation and Hyperalgesia in Neonatal Rats by Systemic Lipopolysaccharide Exposure

“…Consistent with these studies, we found that DEX could alleviate inflammation, both in the serum and the spinal cord, in neonatal rats injected with LPS. As the inhibition of microglial activation and microglial polarization toward the M1 phenotype has contributed to the anti-inflammatory property of DEX in the CNS ( Yeh et al, 2018 ; Gao et al, 2019 ; Meng et al, 2020 ), we next examined the effects of DEX on the expression levels of M1 microglial markers and indeed found that DEX pretreatment decreased the LPS-induced expressions of M1 microglial markers in the spinal cord of neonatal rats. To further confirm the protective effects of DEX on microglia, we sorted microglia from the spinal cord and found that DEX pretreatment decreased LPS-induced expressions of pro-inflammatory cytokines in microglia.…”

Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis

“…In response to any type of pathologic events (injury, infection, and inflammation) or changes in brain homeostasis, microglia rapidly switch to an activated state, undergo substantial morphological, molecular, and functional changes, and produce a broad spectrum of proinflammatory mediators, such as nitric oxide (NO), reactive oxygen species (ROS), and proinflammatory cytokines, including interleukin 1beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), resulting in inflammation-induced neuronal cell damage or death [3]. The immortalized murine BV2 microg-lia have been widely used as an in vitro cell model to investigate the molecular mechanisms underlying microglial activation [4][5][6]. Emerging studies show that microglia activation has protective effects for neurons by attenuating neuronal apoptosis, increasing neurogenesis, and promoting functional recovery.…”