Hayakawa Kazuhide, Mishima Kenichi, Nozako Masanori, Hazekawa Mai, Irie Keiichi, Fujioka Masayuki, Orito Kensuke, Abe Kohji, Hasebe Nobuyoshi, Egashira Nobuaki, Iwasaki Katsunori, Fujiwara Michihiro
Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
J Neurochem. 2007 Sep;102(5):1488-1496. doi: 10.1111/j.1471-4159.2007.04565.x. Epub 2007 Apr 16.
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. Cannabidiol provides potent and long-lasting neuroprotection through an anti-inflammatory CB(1) receptor-independent mechanism, suggesting that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.
我们在4小时小鼠大脑中动脉（MCA）闭塞模型中，将大麻的非精神活性成分大麻二酚的神经保护机制与Δ⁹-四氢大麻酚（Δ⁹-THC）进行了比较，以研究其对梗死的影响。在MCA闭塞后2小时测量皮质中谷氨酸的释放。在再灌注后1小时测量髓过氧化物酶（MPO）和脑血流量。此外，在MCA闭塞后24小时和72小时测定梗死面积和MPO。大麻二酚的神经保护作用不受SR141716或AM630的抑制。大麻二酚的缺血前和缺血后治疗均产生了强效且持久的神经保护作用，而只有Δ⁹-THC的缺血前治疗减少了梗死面积。与Δ⁹-THC不同，大麻二酚不会影响闭塞后皮质中谷氨酸的过量释放。大麻二酚通过抑制再灌注后脑微循环衰竭引起的脑血流量减少，并抑制中性粒细胞中的MPO活性。此外，在大麻二酚治疗组的同侧半球中，MPO免疫阳性细胞的数量减少。大麻二酚通过一种独立于CB₁受体的抗炎机制提供强效且持久的神经保护作用，这表明大麻二酚将具有缓解作用，并为治疗脑血管疾病开辟新的治疗可能性。
