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

Allen, C.L.; Bayraktutan, Ulvi

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.

Citation

Allen, C., & Bayraktutan, U. (2009). Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood–brain barrier hyperpermeability. Diabetes, Obesity and Metabolism, 11(5), https://doi.org/10.1111/j.1463-1326.2008.00987.x

• Journal Article Type: Article
• Publication Date: May 1, 2009
• Deposit Date: Jul 7, 2009
• Publicly Available Date: Jul 7, 2009
• Journal: Diabetes, Obesity and Metabolism
• Print ISSN: 1462-8902
• Electronic ISSN: 1463-1326
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 5
• DOI: https://doi.org/10.1111/j.1463-1326.2008.00987.x
• Public URL: https://nottingham-repository.worktribe.com/output/1013743
• Publisher URL: http://www3.interscience.wiley.com/cgi-bin/fulltext/122209271/HTMLSTART
• Additional Information: The definitive version is available at: www3.interscience.wiley.com