Ku, J. M., Taher, M., Chin, K. Y., Barsby, T., Austin, V., Wong, C. H.Y., Andrews, Z. B., Spencer, S. J. and Miller, A. A. (2016) Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice. Clinical Science, 130(17), pp. 1545-1558. (doi: 10.1042/CS20160077) (PMID:27303049)
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Abstract
The major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, emerging evidence indicates that these peptides may have other functions including neuro- and vaso-protection. Here, we investigated whether post-stroke treatment with acylated ghrelin or des-acylated ghrelin could improve functional and histological endpoints of stroke outcome in mice after transient middle cerebral artery occlusion (tMCAo). We found that des-acylated ghrelin (1 mg/kg) improved neurological and functional performance, reduced infarct and swelling, and decreased apoptosis. In addition, it reduced blood-brain barrier (BBB) disruption in vivo and attenuated the hyper-permeability of mouse cerebral microvascular endothelial cells after oxygen glucose deprivation and reoxygenation (OGD + RO). By contrast, acylated ghrelin (1 mg/kg or 5 mg/kg) had no significant effect on these endpoints of stroke outcome. Next we found that des-acylated ghrelin's vasoprotective actions were associated with increased expression of tight junction proteins (occludin and claudin-5), and decreased cell death. Moreover, it attenuated superoxide production, Nox activity and expression of 3-nitrotyrosine. Collectively, these results demonstrate that post-stroke treatment with des-acylated ghrelin, but not acylated ghrelin, protects against ischaemia/reperfusion-induced brain injury and swelling, and BBB disruption, by reducing oxidative and/or nitrosative damage.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Miller, Dr Alyson |
Authors: | Ku, J. M., Taher, M., Chin, K. Y., Barsby, T., Austin, V., Wong, C. H.Y., Andrews, Z. B., Spencer, S. J., and Miller, A. A. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Clinical Science |
Publisher: | Portland Press |
ISSN: | 0143-5221 |
ISSN (Online): | 1470-8736 |
Published Online: | 14 June 2016 |
Copyright Holders: | Copyright © 2016 The Authors |
First Published: | First published in Clinical Science 130(17):1545-1558 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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