期刊
ACTA PHARMACOLOGICA SINICA
卷 34, 期 1, 页码 119-128出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2012.141
关键词
stroke; permanent focal cerebral ischemia; penumbra; oligodendrocyte precursor cells; neural glial antigen 2 (NG2); tau-1; cannabinoid receptor type 1 (CB1); WIN55,212-2; rimonabant
资金
- National Natural Science Foundation of China [81070967]
- Natural Science Foundation of Jiangsu Province [BK2009296]
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 CBI. 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 CBI 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 CBI and may contribute to its neuroprotective effects.
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