title: WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Yin-quan
authors.initials: YQ
authors.lastname: Fang
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Shu
authors.initials: S
authors.lastname: Song
authors.forename: Lu-yong
authors.initials: LY
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Liao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D048588:Benzoxazines / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D009281:Naphthalenes / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C085348:tau-1 monoclonal antibody; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone