Therapeutic Time Window of Cannabidiol Treatment on Delayed Ischemic Damage via High-Mobility Group Box1-Inhibiting Mechanism
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概要
- 論文の詳細を見る
Cannabidiol decreases cerebral infarction and high-mobility group box1 (HMGB1) in plasma in ischemic early phase. However, plasma HMGB1 levels in ischemic delayed phase reach higher concentration with the progressing brain injury. In this study, we investigated the therapeutic time window of cannabidiol on functional deficits, glial HMGB1 and plasma HMGB1 levels in a 4 h mouse middle cerebral artery (MCA) occlusion model. Cannabidiol-treated mice were divided into 3 groups as follows: group (a) treated from day 1, group (b) treated from day 3, group (c) treated from day 5 after MCA occlusion. Moreover, minocycline, microglia inhibitor, and fluorocitrate, an inhibitor of astroglial metabolism, were used to compare with cannabidiol-treated group. Repeated treatment with cannabidiol from 1 and 3 d at the latest after cerebral ischemia improved functional deficits and survival rates. However, cannabidiol from 5 d could not improve the ischemic damage as well as fluorocitrate-treated group. Moreover, both group (a), group (b) and minocycline but not group (c) and fluorocitrate-treated group had a decrease in the number of Iba1 expressing HMGB1 positive cells and HMGB1 levels in plasma. Cannabidiol may provide therapeutic possibilities for the progressing brain injury via HMGB1-inhibiting mechanism.
著者
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Hayakawa Kazuhide
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Irie Keiichi
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Mishima Kenichi
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Fujiwara Michihiro
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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WATANABE Takuya
Department of Biochemistry, Showa University School of Medicine
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IWASAKI Katsunori
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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FUJIOKA Masayuki
Department of Neurosurgery, Nara Emergency and Critical Care Center
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Fujioka Masayuki
Department Of Clinical Laboratory Daito Central Hospital
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Higuchi Sei
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan
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Sano Kazunori
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Enoki Makiko
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Nakano Takafumi
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Harada Kazuhiko
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Ishikane Shin
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Ikeda Tomoaki
Department of Perinatology, National Cardiovascular Center
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Orito Kensuke
Department of Physiology II, School of Veterinary Medicine, Azabu University
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Enoki Makiko
Department Of Applied Chemistry Faculty Of Engineering Kyusyu University
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Iwasaki Katsunori
Dep. Of Neuropharmacology Fac. Of Pharmaceutical Sciences Fukuoka Univ.
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Irie Keiichi
Department Of Neuropharmacology Faculty Of Pharmaceutical Sciences Fukuoka University
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Ikeda Tomoaki
Department Of Obsterics And Gyneclogy Miyazaki Medical College University Of Miyazaki
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Watanabe Takuya
Department Of Biochemistry Showa University School Of Medicine
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Iwasaki Katsunori
Department Of Mathematical Sciences The University Of Tokyo
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Hayakawa Kazuhide
Department Of Food Science And Technology National Fisheries University
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Mishima Kenichi
Department Of Chemical Engineering Faculty Of Engineering Fukuoka University
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Iwasaki Katunori
Department Of Neuropharmacology Faculty Of Pharmaceutical Sciences Fukuoka University
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Higuchi Sei
Department Of Neuropharmacology Faculty Of Pharmaceutical Sciences Fukuoka University
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Fujiwara Michihiro
Department Of Neuroparmacology Faculty Of Pharmaceutical Sciences Fukuoka University
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Nakano Takafumi
Department Of Neuropharmacology Faculty Of Pharmaceutical Sciences Fukuoka University
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IKEDA Tomoaki
Deparartment of Perinatology, National Cardiovascular Center
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Fujioka Masayuki
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Watanabe Takuya
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Orito Kensuke
Department of Pharmacology, Tohoku University School of Medicine
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