The Cannabinoid-2 Receptor Agonist O-1966 Reverses Postischemic Learning and Memory Deficits Through Anti-Inflammatory Processes

Ischemic stroke is the third leading cause of death and the leading cause of morbidity in the United States. Cognitive deficits, specifically with respect to learning and memory, are a significant contributor to morbidity in stroke patients. Unfortunately, current treatment options must be administered within a thin therapeutic window of the initial infarct. This requirement results in less than 10% of stroke patients being eligible for treatment. There are currently no treatment options that are effective in the subacute phase of the disease and no treatments that are effective in reversing postischemic learning and memory deficits. We sought to examine the potential efficacy of the anti-inflammatory Cannabinoid-2 Receptor Agonist, O-1966, in attenuating infarct expansion and reversing cognitive deficits in the subacute phase of the disease using a photothrombosis model of stroke. Additionally, we sought to characterize the inflammatory response in photothrombosis. Mice were treated with repeated doses of O-1966 or vehicle and were sacrificed at 24 hours and 7 days to study the acute and subacute phase of the disease respectively. Learning and memory testing, immunohistochemistry, and polymerase chain reaction were used to measure the effect of O-1966 on infarct expansion, inflammatory gene expression, and cognitive function. In addition to PCR, flow cytometry was used to characterize the temporal dynamics of inflammation following photothrombosis. Our studies show that O-1966 is effective in the subacute phase in attenuating infarct expansion and proinflammatory gene expression and reversing learning and memory deficits.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2013

Author dc:creator

• Ronca, Rich Daniel

Advisor dc:contributor.advisor

• Tuma, Ronald F. (Ronald Franklin)

Committee members dc:contributor.committeemember

• Eguchi, Satoru
• Heckman, James L.
• Wolfson, Marla R.
• Ward, Sara Jane

• Physiology

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Dc Identifier Other

890207749

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/3490