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.
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September 2016
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Corin protein expression in human renal proximal convoluted tubules as shown by brown staining in immunohistochemistry. See pp. 1655-1664 for further details. Image kindly provided by Qingyu Wu.
Research Article|
July 26 2016
Protective actions of des-acylated ghrelin on brain injury and blood–brain barrier disruption after stroke in mice
Jacqueline M. Ku;
Jacqueline M. Ku
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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Mohammadali Taher;
Mohammadali Taher
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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Kai Yee Chin;
Kai Yee Chin
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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Tom Barsby;
Tom Barsby
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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Victoria Austin;
Victoria Austin
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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Connie H.Y. Wong;
Connie H.Y. Wong
†Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Melbourne, Victoria 3168, Australia
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Zane B. Andrews;
Zane B. Andrews
‡Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia
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Sarah J. Spencer;
Sarah J. Spencer
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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Alyson A. Miller
*Cerebrovascular and Stroke Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
Correspondence: Dr Alyson A. Miller (email alyson.miller@rmit.edu.au).
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Publisher: Portland Press Ltd
Received:
February 02 2016
Revision Received:
May 26 2016
Accepted:
June 13 2016
Accepted Manuscript online:
June 14 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2016) 130 (17): 1545–1558.
Article history
Received:
February 02 2016
Revision Received:
May 26 2016
Accepted:
June 13 2016
Accepted Manuscript online:
June 14 2016
Citation
Jacqueline M. Ku, Mohammadali Taher, Kai Yee Chin, Tom Barsby, Victoria Austin, Connie H.Y. Wong, Zane B. Andrews, Sarah J. Spencer, Alyson A. Miller; Protective actions of des-acylated ghrelin on brain injury and blood–brain barrier disruption after stroke in mice. Clin Sci (Lond) 1 September 2016; 130 (17): 1545–1558. doi: https://doi.org/10.1042/CS20160077
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