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Neurocritical Care

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23-11-2022 | Central Nervous System Trauma | Original work

Dexmedetomidine Alters the Inflammatory Profile of Rat Microglia In Vitro

Authors: Michael C. Scott, Candice M. Haase, Scott D. Olson, Charles S. Cox Jr

Published in: Neurocritical Care | Issue 3/2023

Abstract

Background

Microglia are a primary mediator of the neuroinflammatory response to neurologic injury, such as that in traumatic brain injury. Their response includes changes to their cytokine expression, metabolic profile, and immunophenotype. Dexmedetomidine (DEX) is an α₂ adrenergic agonist used as a sedative in critically ill patients, such as those with traumatic brain injury. Given its pharmacologic properties, DEX may alter the phenotype of inflammatory microglia.

Methods

Primary microglia were isolated from Sprague–Dawley rats and cultured. Microglia were activated using multiple mediators: lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (Poly I:C), and traumatic brain injury damage-associated molecular patterns (DAMP) from a rat that sustained a prior controlled cortical impact injury. After activation, cultures were treated with DEX. At the 24-h interval, the cell supernatant and cells were collected for the following studies: cytokine expression (tumor necrosis factor-α [TNFα], interleukin-10 [IL-10]) via enzyme-linked immunosorbent assay, 6-phosphofructokinase enzyme activity assay, and immunophenotype profiling with flow cytometry. Cytokine expression and metabolic enzyme activity data were analyzed using two-way analysis of variance. Cell surface marker expression was analyzed using FlowJo software.

Results

In LPS-treated cultures, DEX treatment decreased the expression of TNFα from microglia (mean difference = 121.5 ± 15.96 pg/mL; p < 0.0001). Overall, DEX-treated cultures had a lower expression of IL-10 than nontreated cultures (mean difference = 39.33 ± 14.50 pg/mL, p < 0.0001). DEX decreased IL-10 expression in LPS-stimulated microglia (mean difference = 74.93 ± 12.50 pg/mL, p = 0.0039) and Poly I:C-stimulated microglia (mean difference = 23.27 ± 6.405 pg/mL, p = 0.0221). In DAMP-stimulated microglia, DEX decreased the activity of 6-phosphofructokinase (mean difference = 18.79 ± 6.508 units/mL; p = 0.0421). The microglial immunophenotype was altered to varying degrees with different inflammatory stimuli and DEX treatment.

Conclusions

DEX may alter the neuroinflammatory response of microglia. By altering the microglial profile, DEX may affect the progression of neurologic injury.

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Title: Dexmedetomidine Alters the Inflammatory Profile of Rat Microglia In Vitro
Authors: Michael C. Scott
Candice M. Haase
Scott D. Olson
Charles S. Cox Jr
Publication date: 23-11-2022
Publisher: Springer US
Keywords: Central Nervous System Trauma
Cytokines
Published in: Neurocritical Care / Issue 3/2023
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI: https://doi.org/10.1007/s12028-022-01638-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dexmedetomidine Alters the Inflammatory Profile of Rat Microglia In Vitro

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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