{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T12:50:40Z","timestamp":1783774240261,"version":"3.55.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of cerebral blood flow autoregulation. This study identifies a smooth muscle cell autocrine\/paracrine signaling network that augments myogenic tone in a murine model of experimental SAH: it links tumor necrosis factor-\u03b1 (TNF\u03b1), the cystic fibrosis transmembrane conductance regulator, and sphingosine-1-phosphate signaling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Mouse olfactory cerebral resistance arteries were isolated, cannulated, and pressurized for in vitro vascular reactivity assessments. Cerebral blood flow was measured by speckle flowmetry and magnetic resonance imaging. Standard Western blot, immunohistochemical techniques, and neurobehavioral assessments were also used.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>We demonstrate that targeting TNF\u03b1 and sphingosine-1-phosphate signaling in vivo has potential therapeutic application in SAH. Both interventions (1) eliminate the SAH-induced myogenic tone enhancement, but otherwise leave vascular reactivity intact; (2) ameliorate SAH-induced neuronal degeneration and apoptosis; and (3) improve neurobehavioral performance in mice with SAH. Furthermore, TNF\u03b1 sequestration with etanercept normalizes cerebral perfusion in SAH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Vascular smooth muscle cell TNF\u03b1 and sphingosine-1-phosphate signaling significantly enhance cerebral artery tone in SAH; anti-TNF\u03b1 and anti\u2013sphingosine-1-phosphate treatment may significantly improve clinical outcome.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.114.006365","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T14:47:40Z","timestamp":1435934860000},"page":"2260-2270","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Therapeutically Targeting Tumor Necrosis Factor-\u03b1\/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage"],"prefix":"10.1161","volume":"46","author":[{"given":"Kenji","family":"Yagi","sequence":"first","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; Department of Neurosurgery, St. Michael\u2019s Hospital, Toronto, Canada (K.Y., M.S., J.A., R.L.M.); Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (K.Y., M..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy","family":"Lidington","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; Department of Neurosurgery, St. Michael\u2019s Hospital, Toronto, Canada (K.Y., M.S., J.A., R.L.M.); Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (K.Y., M..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoyee","family":"Wan","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; Department of Neurosurgery, St. Michael\u2019s Hospital, Toronto, Canada (K.Y., M.S., J.A., R.L.M.); Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (K.Y., M..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C.","family":"Fares","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; Department of Neurosurgery, St. Michael\u2019s Hospital, Toronto, Canada (K.Y., M.S., J.A., R.L.M.); Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (K.Y., M..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Meissner","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; Department of Neurosurgery, St. Michael\u2019s Hospital, Toronto, Canada (K.Y., M.S., J.A., R.L.M.); Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (K.Y., M..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Sumiyoshi","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; Department of Neurosurgery, St. Michael\u2019s Hospital, Toronto, Canada (K.Y., M.S., J.A., R.L.M.); Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (K.Y., M..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglu","family":"Ai","sequence":"additional","affiliation":[{"name":"From the Department of Physiology (D.L., J.C.F., A.M., S.-S.B.), Physical Sciences, Sunnybrook Research Institute and Medical Biophysics (H.W.), and Heart and Stroke\/Richard Lewar Centre of Excellence for Cardiovascular Research (S.-S.B.), University of Toronto, Toronto, Canada; 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