Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood–brain barrier hyperpermeability

Allen, C.L. and Bayraktutan, Ulvi (2009) Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood–brain barrier hyperpermeability. Diabetes, Obesity and Metabolism, 11 (5). pp. 480-490. ISSN 1462-8902

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Abstract

Aims: Hyperglycaemia (HG), in stroke patients, is associated with worse neurological outcome by compromising endothelial cell function and the blood–brain barrier (BBB) integrity. We have studied the contribution of HG-mediated

generation of oxidative stress to these pathologies and examined whether antioxidants as well as normalization of

glucose levels following hyperglycaemic insult reverse these phenomena.

Methods: Human brain microvascular endothelial cell (HBMEC) and human astrocyte co-cultures were used to simulate

the human BBB. The integrity of the BBB was measured by transendothelial electrical resistance using STX

electrodes and an EVOM resistance meter, while enzyme activities were measured by specific spectrophotometric

assays.

Results: After 5 days of hyperglycaemic insult, there was a significant increase in BBB permeability that was reversed

by glucose normalization. Co-treatment of cells with HG and a number of antioxidants including vitamin C, free radical

scavengers and antioxidant enzymes including catalase and superoxide dismutase mimetics attenuated the detrimental

effects of HG. Inhibition of p38 mitogen-activated protein kinase (p38MAPK) and protein kinase C but not

phosphoinositide 3 kinase (PI3 kinase) also reversed HG-induced BBB hyperpermeability. In HBMEC, HG enhanced

pro-oxidant (NAD(P)H oxidase) enzyme activity and expression that were normalized by reverting to normoglycaemia.

Conclusions: HG impairs brain microvascular endothelial function through involvements of oxidative stress and

several signal transduction pathways.

Item Type: Article
Additional Information: The definitive version is available at: www3.interscience.wiley.com
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
Depositing User: Sayers, Hazel
Date Deposited: 07 Jul 2009 08:42
Last Modified: 15 Aug 2013 07:28
URI: http://eprints.nottingham.ac.uk/id/eprint/1080

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