title: The CB1 antagonist, SR141716A, is protective in permanent photothrombotic cerebral ischemia.
abstract: Modulation of the endocannabinoid system has been shown to have a significant impact on outcomes in animal models of stroke. We have previously reported a protective effect of the CB1 antagonist, SR141716A, in a transient reperfusion mouse model of cerebral ischemia. This protective effect was in part mediated by activation of the 5HT1A receptor. Here we have examined its effect in a mouse model of permanent ischemia induced by photoinjury. The CB1 antagonist was found to be protective in this model. As was the case following transient ischemia reperfusion, SR141716A (5mg/kg) resulted in smaller infarct fractions and stroke volumes when utilized both as a pretreatment and as a post-treatment. In contrast to the effect in a transient ischemia model, the pretreatment effect did not depend on the 5HT1A receptor. Neurological function correlated favorably to the reduction in stroke size when SR141716A was given as a pretreatment. With the incidence of stroke predicted to rise in parallel with an ever aging population, understanding mechanisms underlying ischemia and therapeutics remains a paramount goal of research.
authors.affiliation: Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, Medical Education and Research Building, 8th floor Philadelphia, PA, 19140, United States. Electronic address: zachr@temple.edu.
authors.forename: Zachary Wilmer
authors.initials: ZW
authors.lastname: Reichenbach
authors.affiliation: Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, Medical Education and Research Building, 8th floor Philadelphia, PA, 19140, United States. Electronic address: hongbo.li@temple.edu.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, Medical Education and Research Building, 8th floor Philadelphia, PA, 19140, United States. Electronic address: saraward@temple.edu.
authors.forename: Sara Jane
authors.initials: SJ
authors.lastname: Ward
authors.affiliation: Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, 3500 North Broad Street, Medical Education and Research Building, 8th floor Philadelphia, PA, 19140, United States. Electronic address: tumarf@temple.edu.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Tuma
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D063387:Cannabinoid Receptor Antagonists / Q000008:administration & dosage*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D020521:Stroke / Q000150:complications / Q000473:pathology / Q000517:prevention & control*
chemical_list: D063387:Cannabinoid Receptor Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant
keywords: CB(1) antagonist; Cannabinoid receptor; Cerebral ischemia; Permanent occlusion; Photochemical injury; Stroke