Cabergoline possesses a beneficial effect on blood-brain barrier (BBB) integrity against lipopolysaccharide (LPS)

Sepsis is a disease induced by severe systemic inflammation and contributes to multiple acute organic dysfunctions. It is reported that disrupted blood-brain barrier (BBB) integrity is involved in sepsis-associated encephalopathy (SAE), which can be alleviated by repairing the damaged tight junction...

Full description

Saved in:
Bibliographic Details
Published in:Bioengineered 2021-01, Vol.12 (1), p.8358-8369
Main Authors: You, Lina, Jiang, Haidong
Format: Article
Language:English
Subjects:
Animals
blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
Cabergoline
Cabergoline - administration & dosage
Cabergoline - chemistry
Cabergoline - pharmacology
Cell Line
DKK3
Female
Humans
Lipopolysaccharides - adverse effects
LPS
Male
Mice
Molecular Structure
Permeability - drug effects
Research Paper
sepsis
Sepsis - chemically induced
Sepsis - drug therapy
Sepsis - metabolism
Wnt Signaling Pathway - drug effects
Zonula Occludens-1 Protein - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Sepsis is a disease induced by severe systemic inflammation and contributes to multiple acute organic dysfunctions. It is reported that disrupted blood-brain barrier (BBB) integrity is involved in sepsis-associated encephalopathy (SAE), which can be alleviated by repairing the damaged tight junction structure. Cabergoline is a specific dopamine D2 receptor agonist developed to treat Parkinson's disease and hyperprolactinemia and is reported to exert promising anti-inflammatory properties. The present study aimed to explore the beneficial effect of Cabergoline for the treatment of sepsis. In the animal experiments, mice were separated into 4 groups: sham, LPS (5 mg/kg), Cabergoline (0.1 mg/kg/day), and Cabergoline+LPS. We found that the increased neurological deficits, disrupted BBB integrity, elevated production of inflammatory factors, and declined expression level of zonula occludens-1 (ZO-1) were observed in lipopolysaccharide (LPS)-treated mice, all of which were significantly reversed by the administration of Cabergoline. In the in vitro model, human brain microvascular endothelial cells (HBMECs) were challenged with 1 µg/mL LPS in the presence or absence of Cabergoline (10, 20 μM) for 24 hours. The elevated cell permeability P app value of fluorescein disodium across the HBMECs monolayer and declined trans-endothelial electrical resistance (TEER) in the LPS-treated HBMECs were significantly alleviated by Cabergoline, accompanied by the upregulation of ZO-1. In addition, wnt1 and β-catenin were found downregulated, which was reversed by Cabergoline. Importantly, the protective benefits of Cabergoline were all abolished by the overexpression of Dickkopf 3 (DKK3). Taken together, our data reveal that Cabergoline possessed a protective effect on BBB integrity against LPS.
ISSN:2165-5979
2165-5987
DOI:10.1080/21655979.2021.1987066