Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice

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)

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
• 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