FTY720 Protects Against Ischemia–Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model

Wang, Zifeng; Higashikawa, Kei; Yasui, Hironobu; Kuge, Yuji; Ohno, Yusuke; Kihara, Akio; Midori, Yenari A.; Houkin, Kiyohiro; Kawabori, Masahito

FTY720 Protects Against Ischemia–Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model

Wang, Zifeng; Higashikawa, Kei; Yasui, Hironobu et al.

Translational Stroke Research, 2020, 11, 1103-1116

Permalink : https://hdl.handle.net/2115/79237

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/79237
タイトル	FTY720 Protects Against Ischemia–Reperfusion Injury by Preventing the Redistribution of Tight Junction Proteins and Decreases Inflammation in the Subacute Phase in an Experimental Stroke Model
著者	Wang, Zifeng ; Higashikawa, Kei ; Yasui, Hironobu ; Kuge, Yuji ; Ohno, Yusuke ; Kihara, Akio ; Midori, Yenari A. ; Houkin, Kiyohiro ; Kawabori, Masahito
著者名 Wang, Zifeng
e-Rad_Researcher 10756878 著者名 Higashikawa, Kei
e-Rad_Researcher 10570228 著者名 Yasui, Hironobu
e-Rad_Researcher 70321958 著者名 Kuge, Yuji
e-Rad_Researcher 50611498 著者名 Ohno, Yusuke
e-Rad_Researcher 50333620 著者名 Kihara, Akio
著者名 Midori, Yenari A.
e-Rad_Researcher 90229146 著者名 Houkin, Kiyohiro
e-Rad_Researcher 50399870 著者名 Kawabori, Masahito
言語	英語
キーワード	FTY720
	Sphingosine-1-phosphate receptor
	Brain ischemia–reperfusion
	Blood–brain barrier
	Inflammation
	Apoptosis
発行日	2020-10
出版者	Springer
収録物名	Translational Stroke Research
巻(号)	11
ページ	1103-1116
抄録	Injury due to brain ischemia followed by reperfusion (I/R) may be an important therapeutic target in the era of thrombectomy. FTY720, a widely known sphingosine-1-phosphate receptor agonist, exerts various neuroprotective effects. The aim of this study was to examine the protective effect of FTY720 with respect to I/R injury, especially focusing on blood?brain barrier (BBB) protection and anti-inflammatory effects. Male rats were subjected to transient ischemia and administered vehicle or 0.5 or 1.5 mg/kg of FTY720 immediately before reperfusion. Positron emission tomography (PET) with [18F]DPA-714 was performed 2 and 9 days after the insult to serially monitor neuroinflammation. Bovine and rat brain microvascular endothelial cells (MVECs) were also subjected to oxygen-glucose deprivation (OGD) and reperfusion, and administered FTY720, phosphorylated-FTY720 (FTY720-P), or their inhibitor. FTY720 dose-dependently reduced cell death, the infarct size, cell death including apoptosis, and inflammation. It also ameliorated BBB disruption and neurological deficits compared to in the vehicle group. PET indicated that FTY720 significantly inhibited the worsening of inflammation in later stages. FTY720-P significantly prevented the intracellular redistribution of tight junction proteins but did not increase their mRNA expression. These results suggest that FTY720 can ameliorate I/R injury by protecting the BBB and regulating neuroinflammation.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
権利情報	© The Author(s) 2020
PISSN	1868-4483
EISSN	1868-601X
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1007/s12975-020-00789-x