Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism |
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Authors: | Hayakawa Kazuhide Mishima Kenichi Irie Keiichi Hazekawa Mai Mishima Shohei Fujioka Masayuki Orito Kensuke Egashira Nobuaki Katsurabayashi Shutaro Takasaki Kotaro Iwasaki Katsunori Fujiwara Michihiro |
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Affiliation: | a Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan b Advanced Materials Institute, Fukuoka University, Fukuoka 814-0180, Japan c Department of Veterinary Pharmacology, School of Veterinary Medicine Azabu University, 1-17-17 Fuchinobe, Sagamihara, Kanagawa 229-8501, Japan |
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Abstract: | We examined the cerebroprotective mechanism of cannabidiol, the non-psychoactive component of marijuana, against infarction in a 4-h mouse middle cerebral artery (MCA) occlusion model. Cannabidiol was intraperitoneally administrated immediately before and 3 h after cerebral ischemia. Infarct size and myeloperoxidase (MPO) activity, a marker of neutrophil, monocyte/macropharge, were measured at 24 h after cerebral ischemia. Activated microglia and astrocytes were evaluated by immunostaining. Moreover, high-mobility group box1 (HMGB1) was also evaluated at 1 and 3 days after MCA occlusion. In addition, neurological score and motor coordination on the rota-rod test were assessed at 1 and 3 days after cerebral ischemia. Cannabidiol significantly prevented infarction and MPO activity at 20 h after reperfusion. These effects of cannabidiol were not inhibited by either SR141716 or AM630. Cannabidiol inhibited the MPO-positive cells expressing HMGB1 and also decreased the expression level of HMGB1 in plasma. In addition, cannabidiol decreased the number of Iba1- and GFAP-positive cells at 3 days after cerebral ischemia. Moreover, cannabidiol improved neurological score and motor coordination on the rota-rod test. Our results suggest that cannabidiol inhibits monocyte/macropharge expressing HMGB1 followed by preventing glial activation and neurological impairment induced by cerebral ischemia. Cannabidiol will open new therapeutic possibilities for post-ischemic injury via HMGB1-inhibiting mechanism. |
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Keywords: | Cannabidiol Cerebral ischemia Myeloperoxidase High-mobility group box1 |
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