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.