Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism

Kazuhide Hayakawa, Kenichi Mishima, Keiichi Irie, Mai Hazekawa, Shohei Mishima, Masayuki Fujioka, Kensuke Orito, Nobuaki Egashira, Shutaro Katsurabayashi, Kotaro Takasaki, Katsunori Iwasaki, Michihiro Fujiwara

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1280-1286
Number of pages7
JournalNeuropharmacology
Volume55
Issue number8
DOIs
Publication statusPublished - Dec 1 2008

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Cannabidiol
Brain Ischemia
Wounds and Injuries
Peroxidase
rimonabant
Middle Cerebral Artery Infarction
Infarction
Monocytes
Microglia
Cannabis
Neuroglia
Astrocytes
Reperfusion
Neutrophils

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism. / Hayakawa, Kazuhide; Mishima, Kenichi; Irie, Keiichi; Hazekawa, Mai; Mishima, Shohei; Fujioka, Masayuki; Orito, Kensuke; Egashira, Nobuaki; Katsurabayashi, Shutaro; Takasaki, Kotaro; Iwasaki, Katsunori; Fujiwara, Michihiro.

In: Neuropharmacology, Vol. 55, No. 8, 01.12.2008, p. 1280-1286.

Research output: Contribution to journalArticle

Hayakawa, K, Mishima, K, Irie, K, Hazekawa, M, Mishima, S, Fujioka, M, Orito, K, Egashira, N, Katsurabayashi, S, Takasaki, K, Iwasaki, K & Fujiwara, M 2008, 'Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism', Neuropharmacology, vol. 55, no. 8, pp. 1280-1286. https://doi.org/10.1016/j.neuropharm.2008.06.040
Hayakawa, Kazuhide ; Mishima, Kenichi ; Irie, Keiichi ; Hazekawa, Mai ; Mishima, Shohei ; Fujioka, Masayuki ; Orito, Kensuke ; Egashira, Nobuaki ; Katsurabayashi, Shutaro ; Takasaki, Kotaro ; Iwasaki, Katsunori ; Fujiwara, Michihiro. / Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism. In: Neuropharmacology. 2008 ; Vol. 55, No. 8. pp. 1280-1286.
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