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Neurosci Lett. 2016 Sep 6;630:9-15. doi: 10.1016/j.neulet.2016.07.041. Epub 2016 Jul 21.

The CB1 antagonist, SR141716A, is protective in permanent photothrombotic cerebral ischemia.

Author information

1
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.
2
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.
3
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.
4
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.

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.

KEYWORDS:

CB(1) antagonist; Cannabinoid receptor; Cerebral ischemia; Permanent occlusion; Photochemical injury; Stroke

PMID:
27453059
PMCID:
PMC5002388
DOI:
10.1016/j.neulet.2016.07.041
[Indexed for MEDLINE]
Free PMC Article

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