Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China.
Acta Pharmacol Sin. 2013 Jan;34(1):119-28. doi: 10.1038/aps.2012.141. Epub 2012 Dec 3.
To explore whether the synthetic cannabinoid receptor agonist WIN55,212-2 could protect oligodendrocyte precursor cells (OPCs) in stroke penumbra, thereby providing neuroprotection following permanent focal cerebral ischemia in rats.
Adult male SD rats were subjected to permanent middle cerebral artery occlusion (p-MCAO). The animals were administered WIN55,212-2 at 2 h, and sacrificed at 24 h after the ischemic insult. The infarct volumes and brain swelling were assessed. The expression of cannabinoid receptor type 1 (CB1) in the stroke penumbra was examined using Western blot assay. The pathological changes and proliferation of neural glial antigen 2-positive OPCs (NG2(+) cells) in the stroke penumbra were studied using immunohistochemistry staining.
p-MCAO significantly increased the expression of CB1 within the stroke penumbra with the highest level appearing at 2 h following the ischemic insult. Administration of WIN55,212-2 (9 mg/kg, iv) significantly attenuated the brain swelling, and reduced the infarct volume as well as the number of tau-immunoreactive NG2(+) cells (tau-1(+)/NG2(+) cells) in the stroke penumbra. Moreover, WIN55,212-2 significantly promoted the proliferation of NG2(+) cells in the stroke penumbra and in the ipsilateral subventricular zone at 24 h following the ischemic insult. Administration of the selective CB1 antagonist rimonabant (1 mg/kg, iv) partially blocked the effects caused by WIN55,212-2.
Tau-1 is expressed in NG2(+) cells following permanent focal cerebral ischemic injury. Treatment with WIN55,212-2 reduces the number of tau-1(+)/NG2(+) cells and promotes NG2(+) cell proliferation in the stroke penumbra, which are mediated partially via CB1 and may contribute to its neuroprotective effects.
探讨合成大麻素受体激动剂 WIN55,212-2 是否可以保护缺血半暗带中的少突胶质前体细胞（OPC），从而为大鼠永久性大脑中动脉闭塞（p-MCAO）后提供神经保护作用。
成年雄性 SD 大鼠接受永久性大脑中动脉闭塞（p-MCAO）。动物在缺血性损伤后 2 小时给予 WIN55,212-2，并在 24 小时后处死。评估梗死体积和脑水肿。使用 Western blot 测定法检测缺血半暗带中大麻素受体 1 型（CB1）的表达。使用免疫组织化学染色研究缺血半暗带中神经胶质抗原 2 阳性少突胶质前体细胞（NG2(+)细胞）的病理变化和增殖。
p-MCAO 显著增加了缺血半暗带中的 CB1 表达，在缺血性损伤后 2 小时达到最高水平。给予 WIN55,212-2（9 mg/kg，iv）可显著减轻脑水肿，并减少梗死体积以及缺血半暗带中 tau 免疫反应性 NG2(+)细胞（tau-1(+)/NG2(+)细胞）的数量。此外，WIN55,212-2 在缺血性损伤后 24 小时可显著促进缺血半暗带和同侧侧脑室下区 NG2(+)细胞的增殖。给予选择性 CB1 拮抗剂利莫那班（1 mg/kg，iv）可部分阻断 WIN55,212-2 引起的作用。
tau-1 在永久性局灶性脑缺血损伤后在 NG2(+)细胞中表达。WIN55,212-2 治疗可减少 tau-1(+)/NG2(+)细胞的数量，并促进缺血半暗带中 NG2(+)细胞的增殖，这部分是通过 CB1 介导的，可能有助于其神经保护作用。
