{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:40:40Z","timestamp":1791232840590,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,11,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Inflammation is recognized as an important contributor of ischemia\/reperfusion (I\/R) damage after ischemic stroke. Sphingomyelin synthase 2 (\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2), the key enzyme for the biosynthesis of sphingomyelin, can function as a critical mediator of inflammation. In the present study, we investigated the role of\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 in a mouse model of cerebral I\/R.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Cerebral I\/R was induced by 60\u2010minute transient middle cerebral artery occlusion in\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 knockout (\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2\n              <jats:sup>\u2010\/\u2010<\/jats:sup>\n              ) mice and wild\u2010type mice. Brain injury was determined by neurological deficits and infarct volume at 24 and 72\u00a0hours after transient middle cerebral artery occlusion. Microglia activation and inflammatory factors were detected by immunofluorescence staining, flow cytometry, western blot, and\n              <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n              .\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 deficiency significantly improved neurological function and minimized infarct volume at 72\u00a0hours after transient middle cerebral artery occlusion. The neuroprotective effects of\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 deficiency were associated with (1) suppression of microglia activation through Toll\u2010like receptor 4\/nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells pathway and (2) downregulation of the level of galactin\u20103 and other proinflammatory cytokines. The mechanisms underlying the beneficial effects of\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 deficiency may include altering sphingomyelin components in lipid raft fractions, thus impairing the recruitment of Toll\u2010like receptor 4 to lipid rafts and subsequently reducing Toll\u2010like receptor 4\/myeloid differentiation factor 2 complex formation on the surface of microglia.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 deficiency ameliorated inflammatory injury after cerebral I\/R in mice, and\n              <jats:styled-content style=\"fixed-case\">SMS<\/jats:styled-content>\n              2 may be a key modulator of Toll\u2010like receptor 4\/nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells activation by disturbing the membrane component homeostasis during cerebral I\/R.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.012885","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T10:00:27Z","timestamp":1573639227000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Sphingomyelin Synthase 2 Inhibition Ameliorates Cerebral Ischemic Reperfusion Injury Through Reducing the Recruitment of Toll\u2010Like Receptor 4 to Lipid Rafts"],"prefix":"10.1161","volume":"8","author":[{"given":"Jing","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Neurology Second Hospital of Hebei Medical University Shijiazhuang China"},{"name":"Hebei Collaborative Innovation Center for Cardio\u2010cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis Shijiazhuang 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