Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism
Cannabidiol prevents a post-ischemic injury progressively induced by cerebral ischemia via a high-mobility group box1-inhibiting mechanism
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DOI：
10.1016/j.neuropharm.2008.06.040
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发表时间：
2008-12-01
影响因子：
4.7
通讯作者：
Fujiwara, Michihiro
中科院分区：
文献类型：
--
作者：
Hayakawa, Kazuhide;Mishima, Kenichi;Fujiwara, Michihiro
我们研究了大麻二酚（大麻的非精神活性成分）在4小时小鼠大脑中动脉（MCA）闭塞模型中对梗死的保护机制。大麻二酚在脑缺血前即刻和缺血后3 h腹腔注射。在脑缺血后24 h测量脑体积和髓过氧化物酶（MPO）活性（中性粒细胞、单核细胞/巨噬细胞的标志物）。通过免疫染色评价活化的小胶质细胞和星形胶质细胞。此外，高迁移率族蛋白1（HMGB 1）也在MCA闭塞后第1天和第3天进行了评估。此外，在脑缺血后第1天和第3天评估神经系统评分和旋转杆试验上的运动协调性。Cannabidiol在再灌注后20 h显著防止梗死和MPO活性。大麻二酚的这些作用不受SR 141716或AM 630的抑制。大麻二酚可抑制MPO阳性细胞表达HMGB 1，并降低血浆中HMGB 1的表达水平。此外，大麻二酚在脑缺血后3天减少lba 1和GFAP阳性细胞的数量。此外，大麻二酚改善神经评分和旋转杆测试的运动协调。我们的研究结果表明，大麻二酚抑制单核细胞/巨噬细胞表达HMGB 1，然后防止神经胶质细胞活化和脑缺血引起的神经功能障碍。大麻二酚将通过HMGB 1抑制机制为缺血后损伤开辟新的治疗可能性。(C)2008年由Elsevier Ltd.出版
We examined the cerebroprotective mechanism of cannabidiol, the non-psychoactive component of marijuana, against infarction in a 4-h mouse middle cerebral artery (MCA) occlusion model. Cannabidiol was intraperitoneally administrated immediately before and 3 h after cerebral ischemia. Infarct size and myeloperoxidase (MPO) activity, a marker of neutrophil, monocyte/macropharge, were measured at 24 h after cerebral ischemia. Activated microglia and astrocytes were evaluated by immunostaining. Moreover, high-mobility group box 1 (HMGB1) was also evaluated at I and 3 days after MCA occlusion. In addition, neurological score and motor coordination on the rota-rod test were assessed at 1 and 3 days after cerebral ischemia. Cannabidiol significantly prevented infarction and MPO activity at 20 h after reperfusion. These effects of cannabidiol were not inhibited by either SR141716 or AM630. Cannabidiol inhibited the MPO-positive cells expressing HMGB1 and also decreased the expression level of HMGB1 in plasma. In addition, cannabidiol decreased the number of lba1- and GFAP-positive cells at 3 days after cerebral ischemia. Moreover, cannabidiol improved neurological score and motor coordination on the rota-rod test. Our results suggest that cannabidiol inhibits monocyte/macropharge expressing HMGB1 followed by preventing glial activation and neurological impairment induced by cerebral ischemia. Cannabidiol will open new therapeutic possibilities for post-ischemic injury via HMGB1-inhibiting mechanism. (C) 2008 Published by Elsevier Ltd.