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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

The Effect of Dexamethasone on Lipopolysaccharide-induced Inflammation of Endothelial Cells of the Blood-brain Barrier/Brain Capillaries

Author(s): Tershlin Jeftha, Khayelihle Brian Makhathini and David Fisher*

Volume 20, Issue 3, 2023

Published on: 18 August, 2023

Page: [334 - 345] Pages: 12

DOI: 10.2174/1567202620666230703145707

Price: $65

Abstract

Background: A protective and regulatory barrier between the blood and the brain is constituted by the blood-brain barrier (BBB), which comprises microvascular endothelial cells providing homeostatic regulation of the central nervous system (CNS). Inflammation compromises the BBB and contributes to many CNS disorders. Anti-inflammatory effects are exerted by glucocorticoids (GCs) on a variety of cells. These GCs include dexamethasone (Dex), which is used for the treatment of inflammatory diseases and recently for the treatment of COVID-19.

Aim: The purpose of this study was to determine whether low or high concentrations of Dex can attenuate the inflammatory response induced by lipopolysaccharide (LPS) in the in vitro BBB model.

Methods: Brain endothelial cells (bEnd.5) were cultured and exposed to LPS (100ng/ml) and subsequently co-treated with Dex to investigate whether selected concentrations of Dex (0.1, 5, 10, 20μM) can modulate the inflammatory effects of LPS on bEnd.5 cells. Cell viability, cell toxicity, and cell proliferation were investigated, as well as the monitoring of membrane permeability (Trans Endothelial Electrical Resistance-TEER), and Enzyme-Linked Immune Assay (ELISA) kits were used to identify and quantify the presence of inflammatory cytokines (TNF-α and IL-1β).

Results: Dex, at a lower dosage (0.1μM, but not higher doses), was able to attenuate the inflammatory effects of LPS on bEnd.5 cells. Lower doses of Dex (0.1μM) had no detrimental effects on bEnd.5 cells, while higher Dex doses (5-20μM) decreased bEnd.5 viability, increased bEnd.5 cell toxicity, increased bEnd.5 cell monolayer permeability, and increased proinflammatory cytokine secretion.

Conclusion: These results indicate that treatment of brain vascular inflammation with low doses of Dex should be advocated, while higher doses promote vascular inflammation.

Keywords: Blood-brain barrier, inflammation, tight junctions, permeability, integrity, central nervous system.

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