title: A selective cannabinoid CB2 agonist attenuates damage and improves memory retention following stroke in mice.
abstract: OBJECTIVE
  We have recently demonstrated that treatment with a cannabinoid CB2 agonist was protective in a mouse middle cerebral artery occlusion model of cerebral ischemia/reperfusion injury. The present study aimed to determine whether these protective effects of CB2 agonism would extend to a mouse photoinjury model of permanent ischemia and determine associated alterations in cognition and infarct size.
  
  
  METHODS
  Mice received three injections of the CB2 selective agonist O-1966 or vehicle 1h prior to and 2 and 5days following induction of stroke. Infarct size was assessed at 1, 3, or 7days post-injury and learning and memory effects of injury and O-1966 treatment were assessed on days 6 and 7 using a novel object recognition task and an operant acquisition and retention procedure.
  
  
  RESULTS
  O-1966 treated mice had significantly smaller infarct volumes compared with vehicle treated mice. Photoinjury was also associated with a significant memory impairment on day 7 post-injury, and this deficit was reversed with O-1966 treatment. Surprisingly, sham-operated mice receiving O-1966 treatment showed a significant learning deficit in both the recognition and operant tasks compared with vehicle treated sham mice.
  
  
  CONCLUSIONS
  We conclude that CB2 activation is protective against cognitive deficits and tissue damage following permanent ischemia, but may dysregulate glial or neuronal function of learning and memory circuits in the absence of injury and/or inflammation.
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Ronca
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Myers
authors.affiliation: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Doina
authors.initials: D
authors.lastname: Ganea
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Tuma
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Walker
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA. Electronic address: saraward@temple.edu.
authors.forename: Sara Jane
authors.initials: SJ
authors.lastname: Ward
mesh_terms: D000818:Animals; D000840:Anisoles / Q000627:therapeutic use*; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000473:pathology; D003216:Conditioning, Operant / Q000187:drug effects; D003511:Cyclohexanols; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011597:Psychomotor Performance / Q000187:drug effects; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology*
chemical_list: C531961:1-(4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl)-3-methylcyclohexanol; D000840:Anisoles; D063386:Cannabinoid Receptor Agonists; D003511:Cyclohexanols; D043885:Receptor, Cannabinoid, CB2
keywords: Cannabinoid CB2; Learning and memory; Permanent ischemia; Photoinjury; Stroke