WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats
WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats
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WIN55,212-2 保护大鼠永久性局灶性脑缺血后中风半影区的少突胶质细胞前体细胞
DOI：
10.1038/aps.2012.141
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发表时间：
2013-01-01
影响因子：
8.2
通讯作者：
Liao, Hong
中科院分区：
文献类型：
--
作者：
Sun, Jing;Fang, Yin-quan;Liao, Hong
目的：探讨合成大麻素受体激动剂WIN55,212-2能否保护中风半暗带少突胶质细胞前体细胞（OPCs），从而对大鼠永久性局灶性脑缺血后提供神经保护。方法：对成年雄性SD大鼠进行永久性大脑中动脉闭塞（p-MCAO）。在缺血性损伤后2小时对动物施用WIN55,212-2，并在24小时处死。评估梗塞体积和脑肿胀。使用蛋白质印迹法检测中风半暗带中 1 型大麻素受体 (CB1) 的表达。采用免疫组织化学染色方法研究中风半暗带神经胶质抗原2阳性OPCs（NG2(+)细胞）的病理变化和增殖情况。结果：p-MCAO显着增加中风半暗带内CB1的表达，最高水平出现在缺血损伤后2小时。给予WIN55,212-2（9 mg/kg，静脉注射）显着减轻脑肿胀，减少梗塞体积以及中风半影中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小时显着促进中风半暗带和同侧室下区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引起的效应。结论：永久性局灶性脑缺血损伤后NG2(+)细胞中表达Tau-1。 WIN55,212-2治疗可减少中风半暗带中tau-1(+)/NG2(+)细胞的数量并促进NG2(+)细胞增殖，这部分是通过CB1介导的，可能有助于其神经保护作用。
Aim: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.Methods: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.Results: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.Conclusion: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.