WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats |
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Authors: | Jing Sun Yin-quan Fang Hong Ren Tao Chen Jing-jing Guo Jun Yan Shu Song Lu-yong Zhang Hong Liao |
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Institution: | 1.Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China;2.Department of Pathology, Yancheng City No 1 People''s Hospital, Yancheng 224001, China;3.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China |
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Abstract: | 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. |
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Keywords: | 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 |
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