Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism

被引:70
作者
Hayakawa, Kazuhide
Mishima, Kenichi
Nozako, Masanori
Hazekawa, Mai
Irie, Keiichi
Fujioka, Masayuki
Orito, Kensuke
Abe, Kohji
Hasebe, Nobuyoshi
Egashira, Nobuaki
Iwasaki, Katsunori
Fujiwara, Michihiro
机构
[1] Fukuoka Univ, Fac Pharmaceut Sci, Dept Neuropharmacol, Fukuoka 8140180, Japan
[2] Fukuoka Univ, Adv Mat Inst, Fukuoka, Japan
[3] Dev Res Labs, Dept Drug SAfety Evaluat, Osaka, Japan
[4] Sch Vet Med, Dept Vet Pharmacol, Kanagawa, Japan
关键词
cannabidiol; cannabinoid; cerebral blood flow; cerebral ischemia; glutamate; myeloperoxidase;
D O I
10.1111/j.1471-4159.2007.04565.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We examined the neuroprotective mechanism of cannabidiol, non-psychoactive component of marijuana, on the infarction in a 4 h mouse middle cerebral artery (MCA) occlusion model in comparison with Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Release of glutamate in the cortex was measured at 2 h after MCA occlusion. Myeloperoxidase (MPO) and cerebral blood flow were measured at 1 h after reperfusion. In addition, infarct size and MPO were determined at 24 and 72 h after MCA occlusion. The neuroprotective effect of cannabidiol was not inhibited by either SR141716 or AM630. Both pre- and post-ischemic treatment with cannabidiol resulted in potent and long-lasting neuroprotection, whereas only pre-ischemic treatment with Delta(9)-THC reduced the infarction. Unlike Delta(9)-THC, cannabidiol did not affect the excess release of glutamate in the cortex after occlusion. Cannabidiol suppressed the decrease in cerebral blood flow by the failure of cerebral microcirculation after reperfusion and inhibited MPO activity in neutrophils. Furthermore, the number of MPO-immunopositive cells was reduced in the ipsilateral hemisphere in cannabidiol-treated group. Cannbidiol provides potent and long-lasting neuroprotection through an anti-inflammatory CB1 receptor-independent mechanism, suggesting that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.
引用
收藏
页码:1488 / 1496
页数:9
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