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Activation of AMPK improves lipopolysaccharide-induced dysfunction of the blood-brain barrier in mice.
- Source :
-
Brain injury [Brain Inj] 2015; Vol. 29 (6), pp. 777-84. Date of Electronic Publication: 2015 Mar 20. - Publication Year :
- 2015
-
Abstract
- Primary Objective: Lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB) in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying disruption of the BBB in LPS-induced sepsis.<br />Research Design: Both in vitro and in vivo experiments were designed to test the role of AMP-activated protein kinase (AMPK) in LPS-induced BBB dysfunction.<br />Methods and Procedures: Human brain microvascular endothelial cells (HBMECs) were cultured. The protein expressions were detected by western blot. BBB integrity was determined by Evans Blue.<br />Main Outcomes and Results: LPS (1 μg ml(-1)) dramatically increased the permeability of the BBB and the ROS productions, as well as reducing the expression levels of occludin and claudin-5 in cultured HBMECs. Inhibition of NAD(P)H oxidase by apocynin or up-regulation of AMPK reversed the LPS-induced abnormities in HBMECs. In LPS-induced sepsis in mice, it was found that LPS dramatically increased NAD(P)H oxidase protein expressions and ROS productions in the brain and disrupted BBB function assayed by Evans blue staining, which were abolished by AICAR treatment.<br />Conclusions: It is concluded that AMPK activation improves the functions of the BBB impaired by LPS through suppression of NAD(P)H oxidase-derived ROS in mice.
- Subjects :
- Animals
Blood-Brain Barrier drug effects
Brain blood supply
Brain metabolism
Cell Membrane Permeability drug effects
Cells, Cultured
Endothelial Cells drug effects
Endothelial Cells enzymology
Humans
Lipopolysaccharides pharmacology
Male
Mice
NADPH Oxidases metabolism
Reactive Oxygen Species metabolism
Sepsis chemically induced
Sepsis pathology
Tight Junction Proteins
AMP-Activated Protein Kinases metabolism
Blood-Brain Barrier metabolism
Sepsis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-301X
- Volume :
- 29
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Brain injury
- Publication Type :
- Academic Journal
- Accession number :
- 25794165
- Full Text :
- https://doi.org/10.3109/02699052.2015.1004746