Therapeutic time window of cannabidiol treatment on delayed ischemic damage via high-mobility group box1-inhibiting mechanism.
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.
Hayakawa
Kazuhide
K
Department of Neuropharmacology, Fukuoka University, Japan.
Irie
Keiichi
K
Sano
Kazunori
K
Watanabe
Takuya
T
Higuchi
Sei
S
Enoki
Makiko
M
Nakano
Takafumi
T
Harada
Kazuhiko
K
Ishikane
Shin
S
Ikeda
Tomoaki
T
Fujioka
Masayuki
M
Orito
Kensuke
K
Iwasaki
Katsunori
K
Mishima
Kenichi
K
Fujiwara
Michihiro
M
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
D015415:Biomarkers; D024243:HMGB1 Protein; D002185:Cannabidiol