Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion

Abstract Chronic cerebral hypoperfusion is a major cause of age-related vascular cognitive impairment. A well-characterised mouse model has shown that hypoperfusion results in gliovascular and white matter damage and impaired spatial working memory. In this study, we assessed whether cilostazol, a p...

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Autores principales:	Akihiro Kitamura, Yasmina Manso, Jessica Duncombe, James Searcy, Juraj Koudelka, Margaret Binnie, Scott Webster, Ross Lennen, Maurits Jansen, Ian Marshall, Masafumi Ihara, Raj N. Kalaria, Karen Horsburgh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a99c822285fe43d893ff1f0c5c5d7bd5
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spelling	oai:doaj.org-article:a99c822285fe43d893ff1f0c5c5d7bd52021-12-02T12:31:58ZLong-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion10.1038/s41598-017-04082-02045-2322https://doaj.org/article/a99c822285fe43d893ff1f0c5c5d7bd52017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04082-0https://doaj.org/toc/2045-2322Abstract Chronic cerebral hypoperfusion is a major cause of age-related vascular cognitive impairment. A well-characterised mouse model has shown that hypoperfusion results in gliovascular and white matter damage and impaired spatial working memory. In this study, we assessed whether cilostazol, a phosphodiesterase III inhibitor, could protect against these changes. Adult, male C57Bl/6J mice were subjected to bilateral common carotid artery stenosis or a sham operation and fed normal or cilostazol diet for three months. Cilostazol treatment reduced the impairment in working memory and white matter function after hypoperfusion. Endothelial adhesion molecules and gliosis, increased after hypoperfusion, were ameliorated with cilostazol treatment. Interestingly, the improvement in working memory was closely correlated with reduced microglia and endothelial adhesion molecules. Further, the number of stroke lesions after hypoperfusion was reduced in the cilostazol-treated group. Altogether cilostazol showed potential to ameliorate the gliovascular damage and working memory impairments after hypoperfusion possibly via endothelial protection supporting its potential use in the treatment of vascular cognitive impairment.Akihiro KitamuraYasmina MansoJessica DuncombeJames SearcyJuraj KoudelkaMargaret BinnieScott WebsterRoss LennenMaurits JansenIan MarshallMasafumi IharaRaj N. KalariaKaren HorsburghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akihiro Kitamura Yasmina Manso Jessica Duncombe James Searcy Juraj Koudelka Margaret Binnie Scott Webster Ross Lennen Maurits Jansen Ian Marshall Masafumi Ihara Raj N. Kalaria Karen Horsburgh Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
description	Abstract Chronic cerebral hypoperfusion is a major cause of age-related vascular cognitive impairment. A well-characterised mouse model has shown that hypoperfusion results in gliovascular and white matter damage and impaired spatial working memory. In this study, we assessed whether cilostazol, a phosphodiesterase III inhibitor, could protect against these changes. Adult, male C57Bl/6J mice were subjected to bilateral common carotid artery stenosis or a sham operation and fed normal or cilostazol diet for three months. Cilostazol treatment reduced the impairment in working memory and white matter function after hypoperfusion. Endothelial adhesion molecules and gliosis, increased after hypoperfusion, were ameliorated with cilostazol treatment. Interestingly, the improvement in working memory was closely correlated with reduced microglia and endothelial adhesion molecules. Further, the number of stroke lesions after hypoperfusion was reduced in the cilostazol-treated group. Altogether cilostazol showed potential to ameliorate the gliovascular damage and working memory impairments after hypoperfusion possibly via endothelial protection supporting its potential use in the treatment of vascular cognitive impairment.
format	article
author	Akihiro Kitamura Yasmina Manso Jessica Duncombe James Searcy Juraj Koudelka Margaret Binnie Scott Webster Ross Lennen Maurits Jansen Ian Marshall Masafumi Ihara Raj N. Kalaria Karen Horsburgh
author_facet	Akihiro Kitamura Yasmina Manso Jessica Duncombe James Searcy Juraj Koudelka Margaret Binnie Scott Webster Ross Lennen Maurits Jansen Ian Marshall Masafumi Ihara Raj N. Kalaria Karen Horsburgh
author_sort	Akihiro Kitamura
title	Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
title_short	Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
title_full	Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
title_fullStr	Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
title_full_unstemmed	Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
title_sort	long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a99c822285fe43d893ff1f0c5c5d7bd5
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Long-term cilostazol treatment reduces gliovascular damage and memory impairment in a mouse model of chronic cerebral hypoperfusion

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