title: Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism.
abstract: 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.
authors.affiliation: Department of Neuropharmacology, Fukuoka University, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Irie
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sano
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Sei
authors.initials: S
authors.lastname: Higuchi
authors.forename: Makiko
authors.initials: M
authors.lastname: Enoki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakano
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Harada
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikane
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujioka
authors.forename: Kensuke
authors.initials: K
authors.lastname: Orito
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D002185:Cannabidiol / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000097:blood*; D008297:Male; D051379:Mice; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D002185:Cannabidiol