{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:38:06Z","timestamp":1790267886707,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,11,12]],"date-time":"2010-11-12T00:00:00Z","timestamp":1289520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The sphingosine\u20101\u2010phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischemia. To assess the translational significance of these findings, we asked whether fingolimod improved long\u2010term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We used rodent models of middle cerebral artery occlusion and cell\u2010culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod\u2010treated mice had fewer activated neutrophils, microglia\/macrophages, and intercellular adhesion molecule\u20101 (ICAM\u20101)\u2010positive blood vessels. Fingolimod\u2010treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM\u20101 expression in brain endothelial cells stimulated by tumor necrosis factor alpha.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation:<\/jats:title>\n                    <jats:p>These findings suggest that anti\u2010inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment. ANN NEUROL, 2010<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.22186","type":"journal-article","created":{"date-parts":[[2010,11,12]],"date-time":"2010-11-12T10:59:21Z","timestamp":1289559561000},"page":"119-129","source":"Crossref","is-referenced-by-count":246,"title":["Fingolimod provides long\u2010term protection in rodent models of cerebral ischemia"],"prefix":"10.1002","volume":"69","author":[{"given":"Ying","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muge","family":"Yemisci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung\u2010Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai Ming","family":"Yung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwa 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