title: Cannabinoid CB(2) receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model.
abstract: Cannabinoid CB(2) Receptor (CB(2)) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB(2) agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB(2) agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB(2) agonists significantly decreased cerebral infarction (30%) and improved motor function (P<0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P<0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB(2) agonists administered either at 1 h before or after MCAO (P<0.05). CB(2) activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.
authors.affiliation: Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Billy R
authors.initials: BR
authors.lastname: Martin
authors.forename: Martin W
authors.initials: MW
authors.lastname: Adler
authors.forename: Raj K
authors.initials: RK
authors.lastname: Razdan
authors.forename: Jack I
authors.initials: JI
authors.lastname: Jallo
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Tuma
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002448:Cell Adhesion / Q000276:immunology; D002544:Cerebral Infarction / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism; D036904:Leukocyte Rolling / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism*; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D043885:Receptor, Cannabinoid, CB2