Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

Lu, Yong; Ding, Xiaonan; Wu, Xin; Huang, Shaoqiang

doi:10.1111/fcp.12508

Cited by 28 publications

(21 citation statements)

References 28 publications

(39 reference statements)

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“…Ketamine’s effects on inflammatory T-cells, nitric oxide production, and numerous ion channels and receptors may also be associated with its anti-inflammatory properties [ 7 ]. Ketamine also reduces Ca 2+ levels and inhibits CaMKII phosphorylation through NMDA blockade, and thus inhibits NF-κB translocation [ 76 ]. By interfering with both pro- and anti-inflammatory cytokine production, ketamine may act to realign the immune system to homeostasis following an inflammatory insult [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague–Dawley rats

Spencer

Berman

Boese

et al. 2022

J Neuroinflammation

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Background Ketamine, a multimodal dissociative anesthetic drug, is widely used as an analgesic following traumatic injury. Although ketamine may produce anti-inflammatory effects when administered after injury, the immunomodulatory properties of intravenous (IV) ketamine in a non-inflammatory condition are unclear. In addition, most preclinical studies use an intraperitoneal (IP) injection of ketamine, which limits its clinical translation as patients usually receive an IV ketamine infusion after injury. Methods Here, we administered sub-anesthetic doses of a single IV ketamine infusion (0, 10, or 40 mg/kg) to male and female Sprague–Dawley rats over a 2-h period. We collected blood samples at 2- and 4-h post-ketamine infusion to determine plasma inflammatory cytokine levels using multiplex immunoassays. Results The 10 mg/kg ketamine infusion reduced spontaneous locomotor activity in male and female rats, while the 40 mg/kg infusion stimulated activity in female, but not male, rats. The IV ketamine infusion produced dose-dependent and sex-specific effects on plasma inflammatory cytokine levels. A ketamine infusion reduced KC/GRO and tumor necrosis factor alpha (TNF-α) levels in both male and female rats, interleukin-6 (IL-6) levels in female rats, and interleukin-10 (IL-10) levels in male rats. However, most cytokine levels returned to control levels at 4-h post-infusion, except for IL-6 levels in male rats and TNF-α levels in female rats, indicating a different trajectory of certain cytokine changes over time following ketamine administration. Conclusions The current findings suggest that sub-anesthetic doses of an IV ketamine infusion may produce sex-related differences in the effects on peripheral inflammatory markers in rodents, and further research is warranted to determine potential therapeutic effects of an IV ketamine infusion in an inflammatory condition.

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Section: Discussionmentioning

confidence: 99%

Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague–Dawley rats

Spencer

Berman

Boese

et al. 2022

J Neuroinflammation

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“…Good Mg status may also aid control of inflammation-dietary Mg intake correlates inversely with serum C-reactive protein, and supplemental Mg has been found to decrease this parameter [271,272]. Possibly, this reflects the fact that calcium/calmodulin-dependent kinase-II activation exerts an up-regulatory effect on NF-kappa B activity in macrophages, an effect also seen in microglia [273,274]. These considerations suggest that ensuring good Mg status with a whole-food diet and/or supplementation may provide a measure of protection from AD.…”

Section: Magnesium Deficiency May Up-regulate Amyloid β Neurotoxicitymentioning

confidence: 99%

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

McCarty

DiNicolantonio

Lerner

2021

IJMS

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Oxidative stress and increased cytoplasmic calcium are key mediators of the detrimental effects on neuronal function and survival in Alzheimer’s disease (AD). Pathways whereby these perturbations arise, and then prevent dendritic spine formation, promote tau hyperphosphorylation, further amplify amyloid β generation, and induce neuronal apoptosis, are described. A comprehensive program of nutraceutical supplementation, comprised of the NADPH oxidase inhibitor phycocyanobilin, phase two inducers, the mitochondrial antioxidant astaxanthin, and the glutathione precursor N-acetylcysteine, may have important potential for antagonizing the toxic effects of amyloid β on neurons and thereby aiding prevention of AD. Moreover, nutraceutical antioxidant strategies may oppose the adverse impact of amyloid β oligomers on astrocyte clearance of glutamate, and on the ability of brain capillaries to export amyloid β monomers/oligomers from the brain. Antioxidants, docosahexaenoic acid (DHA), and vitamin D, have potential for suppressing microglial production of interleukin-1β, which potentiates the neurotoxicity of amyloid β. Epidemiology suggests that a health-promoting lifestyle, incorporating a prudent diet, regular vigorous exercise, and other feasible measures, can cut the high risk for AD among the elderly by up to 60%. Conceivably, complementing such lifestyle measures with long-term adherence to the sort of nutraceutical regimen outlined here may drive down risk for AD even further.

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“…Microglia are encephalic cells that are local macrophages of the central nervous system and play an essential role in cerebral immune function. Microglial inflammation induced pro‐inflammatory cytokines and pro‐inflammatory enzymes expression , thus resulting in inflammation‐induced neuronal cell death. Recently, increased intracellular glycolysis was indicated to participate in LPS‐mediated immune cells and microglia inflammation .…”

Section: Introductionmentioning

confidence: 99%

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

Meng

Duan

et al. 2019

Fundamemntal Clinical Pharma

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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.

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Ketamine inhibits LPS‐mediated BV2 microglial inflammation via NMDA receptor blockage

Cited by 28 publications

References 28 publications

Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague–Dawley rats

Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague–Dawley rats

A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

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

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