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Lipoxin A4<\/jats:sub> (LXA<\/jats:styled-content>4<\/jats:sub>) is an anti\u2010inflammatory, pro\u2010resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA<\/jats:styled-content>4<\/jats:sub> is rapidly inactivated, potent analogs have been synthesized, including BML<\/jats:styled-content>\u2010111. We hypothesized that post\u2010ischemic, intravenous treatment with BML<\/jats:styled-content>\u2010111 for 1\u00a0week would provide neuroprotection and reduce neurobehavioral deficits at 4\u00a0weeks after ischemic stroke in rats. Additionally, we investigated the potential protective mechanisms of BML<\/jats:styled-content>\u2010111 on the post\u2010stroke molecular and cellular profile.<\/jats:p><\/jats:sec>Methods<\/jats:title>A total of 133 male Sprague\u2010Dawley rats were subjected to 90\u00a0min of transient middle cerebral artery occlusion (MCAO<\/jats:styled-content>) and BML<\/jats:styled-content>\u2010111 administration was started at the time of reperfusion. Two methods of week\u2010long BML<\/jats:styled-content>\u2010111 intravenous administration were tested: continuous infusion via ALZET<\/jats:styled-content>\u00ae<\/jats:sup> osmotic pumps (1.25 and 3.75\u00a0\u03bcg\u00a0\u03bcl\u22121<\/jats:sup>\u00a0hr\u22121<\/jats:sup>), or freshly prepared daily single injections (0.3, 1, and 3\u00a0mg\/kg). We report for the first time on the stability of BML<\/jats:styled-content>\u2010111 and characterized an optimal dose and a dosing schedule for the administration of BML<\/jats:styled-content>\u2010111.<\/jats:p><\/jats:sec>Results<\/jats:title>One week of BML<\/jats:styled-content>\u2010111 intravenous injections did not reduce infarct size or improve behavioral deficits 4\u00a0weeks after ischemic stroke. However, post\u2010ischemic treatment with BML<\/jats:styled-content>\u2010111 did elicit early protective effects as demonstrated by a significant reduction in infarct volume and improved sensorimotor function at 1\u00a0week after stroke. This protection was associated with reduced pro\u2010inflammatory cytokine and chemokine levels, decreased M1 CD<\/jats:styled-content>40+ macrophages, and increased alternatively activated, anti\u2010inflammatory M2 microglia\/macrophage cell populations in the post\u2010ischemic brain.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These data suggest that targeting the endogenous LXA<\/jats:styled-content>4<\/jats:sub> pathway could be a promising therapeutic strategy for the treatment of ischemic stroke. More work is necessary to determine whether a different dosing regimen or more stable LXA<\/jats:styled-content>4<\/jats:sub> analogs could confer long\u2010term protection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.688","type":"journal-article","created":{"date-parts":[[2017,4,12]],"date-time":"2017-04-12T10:46:40Z","timestamp":1491994000000},"source":"Crossref","is-referenced-by-count":50,"title":["Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4<\/sub> analog: Protective mechanisms and long\u2010term effects on neurological recovery"],"prefix":"10.1002","volume":"7","author":[{"given":"Kimberly E.","family":"Hawkins","sequence":"first","affiliation":[{"name":"Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly M.","family":"DeMars","sequence":"additional","affiliation":[{"name":"Department of Neuroscience McKnight Brain Institute 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