{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:33:23Z","timestamp":1790390003670,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Perihemorrhagic edema (PHE) is associated with poor outcome after intracerebral hemorrhage (ICH). Infiltration of immune cells is considered a major contributor of PHE. Recent studies suggest that immunomodulation via S1PR (sphingosine-1-phosphate receptor) modulators improve outcome in ICH. Siponimod, a selective modulator of sphingosine 1-phosphate receptors type 1 and type 5, demonstrated an excellent safety profile in a large study of patients with multiple sclerosis. Here, we investigated the impact of siponimod treatment on perihemorrhagic edema, neurological deficits, and survival in a mouse model of ICH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>ICH was induced by intracranial injection of 0.075 U of bacterial collagenase in 123 mice. Mice were randomly assigned to different treatment groups: vehicle, siponimod given as a single dosage 30 minutes after the operation or given 3\u00d7 for 3 consecutive days starting 30 minutes after operation. The primary outcome of our study was evolution of PHE measured by magnetic resonance-imaging on T2-maps 72 hours after ICH, secondary outcomes included evolution of PHE 24 hours after ICH, survival and neurological deficits, as well as effects on circulating blood cells and body weight.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              Siponimod significantly reduced PHE measured by magnetic resonance imaging (\n              <jats:italic>P<\/jats:italic>\n              =0.021) as well as wet-dry method (\n              <jats:italic>P<\/jats:italic>\n              =0.04) 72 hours after ICH. Evaluation of PHE 24 hours after ICH showed a tendency toward attenuated brain edema in the low-dosage group (\n              <jats:italic>P<\/jats:italic>\n              =0.08). Multiple treatments with siponimod significantly improved neurological deficits measured by Garcia Score (\n              <jats:italic>P<\/jats:italic>\n              =0.03). Survival at day 10 was improved in mice treated with multiple dosages of siponimod (\n              <jats:italic>P<\/jats:italic>\n              =0.037). Mice treated with siponimod showed a reduced weight loss after ICH (\n              <jats:italic>P<\/jats:italic>\n              =0.036).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Siponimod (BAF-312) attenuated PHE after ICH, increased survival, and reduced ICH-induced sensorimotor deficits in our experimental ICH-model. Findings encourage further investigation of inflammatory modulators as well as the translation of BAF-312 to a human study of ICH patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.119.027134","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T09:00:28Z","timestamp":1569574828000},"page":"3246-3254","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Siponimod (BAF-312) Attenuates Perihemorrhagic Edema And Improves Survival in Experimental Intracerebral Hemorrhage"],"prefix":"10.1161","volume":"50","author":[{"given":"Tobias","family":"Bobinger","sequence":"first","affiliation":[{"name":"From the Department of Neurology (T.B., A.M., P.B., V.B., M.I.S., S.S.R., R.A.L., S.S., H.B.H.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatol","family":"Manaenko","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (T.B., A.M., P.B., V.B., M.I.S., S.S.R., R.A.L., S.S., H.B.H.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Burkardt","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (T.B., A.M., P.B., V.B., M.I.S., S.S.R., R.A.L., S.S., H.B.H.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Beuscher","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (T.B., A.M., P.B., V.B., M.I.S., S.S.R., R.A.L., S.S., H.B.H.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian I.","family":"Spr\u00fcgel","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (T.B., A.M., P.B., V.B., M.I.S., S.S.R., R.A.L., S.S., H.B.H.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian S.","family":"Roeder","sequence":"additional","affiliation":[{"name":"From the Department of Neurology (T.B., A.M., P.B., V.B., M.I.S., S.S.R., R.A.L., S.S., H.B.H.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"B\u00e4uerle","sequence":"additional","affiliation":[{"name":"Department of Radiology (T.B., L.S., A.M.N.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Seyler","sequence":"additional","affiliation":[{"name":"Department of Radiology (T.B., L.S., A.M.N.), University of Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin M.","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Radiology (T.B., L.S., A.M.N.), University of Erlangen, 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