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Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism.
Neuropharmacology. 2008 Dec; 55(8):1280-6.N

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 3h after cerebral ischemia. Infarct size and myeloperoxidase (MPO) activity, a marker of neutrophil, monocyte/macropharge, were measured at 24h 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 20h 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.

Authors+Show Affiliations

Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18634812

Citation

Hayakawa, Kazuhide, et al. "Cannabidiol Prevents a Post-ischemic Injury Progressively Induced By Cerebral Ischemia Via a High-mobility Group Box1-inhibiting Mechanism." Neuropharmacology, vol. 55, no. 8, 2008, pp. 1280-6.
Hayakawa K, Mishima K, Irie K, et al. Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism. Neuropharmacology. 2008;55(8):1280-6.
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, 55(8), 1280-6. https://doi.org/10.1016/j.neuropharm.2008.06.040
Hayakawa K, et al. Cannabidiol Prevents a Post-ischemic Injury Progressively Induced By Cerebral Ischemia Via a High-mobility Group Box1-inhibiting Mechanism. Neuropharmacology. 2008;55(8):1280-6. PubMed PMID: 18634812.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism. AU - Hayakawa,Kazuhide, AU - Mishima,Kenichi, AU - Irie,Keiichi, AU - Hazekawa,Mai, AU - Mishima,Shohei, AU - Fujioka,Masayuki, AU - Orito,Kensuke, AU - Egashira,Nobuaki, AU - Katsurabayashi,Shutaro, AU - Takasaki,Kotaro, AU - Iwasaki,Katsunori, AU - Fujiwara,Michihiro, Y1 - 2008/06/27/ PY - 2008/01/29/received PY - 2008/03/09/revised PY - 2008/06/10/accepted PY - 2008/7/19/pubmed PY - 2009/4/16/medline PY - 2008/7/19/entrez SP - 1280 EP - 6 JF - Neuropharmacology JO - Neuropharmacology VL - 55 IS - 8 N2 - 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 3h after cerebral ischemia. Infarct size and myeloperoxidase (MPO) activity, a marker of neutrophil, monocyte/macropharge, were measured at 24h 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 20h 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. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/18634812/Cannabidiol_prevents_a_post_ischemic_injury_progressively_induced_by_cerebral_ischemia_via_a_high_mobility_group_box1_inhibiting_mechanism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(08)00197-4 DB - PRIME DP - Unbound Medicine ER -