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WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats.
MedLine Citation:
PMID:  23202804     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
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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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-03
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  -     ISSN:  1745-7254     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
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