{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:14:56Z","timestamp":1791094496571,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,4,3]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Activated protein C (APC) contributes to systemic anticoagulant and anti-inflammatory activities. APC may reduce organ damage by inhibiting thrombin generation and leukocyte activation. Neutrophils and cerebrovascular thrombosis contribute to ischemic neuronal injury, suggesting that APC may be a potential protective agent for stroke.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014We examined the effects of APC in a murine model of focal ischemia. After middle cerebral artery occlusion\/reperfusion, the average survival time in controls was 13.6 hours. Animals that received purified human plasma\u2013derived APC 2 mg\/kg IV either 15 minutes before or 10 minutes after stroke induction survived 24 hours and were killed for neuropathological analysis. APC 2 mg\/kg given before or after onset of ischemia restored cerebral blood flow, reduced brain infarct volume (59% to 69%;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.003) and brain edema (50% to 61%;\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), eliminated brain infiltration with neutrophils, and reduced the number of fibrin-positive cerebral vessels by 57% (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05) and 25% (nonsignificant), respectively. The neuroprotective effect of APC was dose-dependent and associated with significant inhibition of ICAM-1 expression on ischemic cerebral blood vessels (eg, 61% inhibition with 2 mg\/kg APC). Intracerebral bleeding was not observed with APC.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014APC exerts anti-inflammatory, antithrombotic, and neuroprotective effects in stroke. Central effects of APC are likely to be related to improved maintenance of the blood-brain barrier to neutrophils and to reduced microvascular obstructions and fibrin deposition.\n          <\/jats:p>","DOI":"10.1161\/01.cir.103.13.1799","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:09:32Z","timestamp":1339459772000},"page":"1799-1805","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":168,"title":["Anti-Inflammatory, Antithrombotic, and Neuroprotective Effects of Activated Protein C in a Murine Model of Focal Ischemic Stroke"],"prefix":"10.1161","volume":"103","author":[{"given":"Masayoshi","family":"Shibata","sequence":"first","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Ram","family":"Kumar","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Amar","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Hofman","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berislav V.","family":"Zlokovic","sequence":"additional","affiliation":[{"name":"From the Department of Neurosurgery (M.S., S.R.K., A.A.) and the Department of Pathology (F.H.), University of Southern California, Los Angeles; the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla (J.A.F., J.H.G.), Calif; and the Division of Neurovascular Biology and the Department of Neurosurgery, Center for Aging and Developmental Biology, University of Rochester Medical Center (B.V.Z.), Rochester, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/378337a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.09.110193.000245"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615840"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.12.2304"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.11.3139"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(98)00135-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112902"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.2.364.364"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.3781.012k18_3781_3787"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.2.642.bloodjournal872642"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.8.3664"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.7.736"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.11.2005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.7.1163"},{"key":"e_1_3_2_16_2","first-page":"256","volume":"125","year":"1996","unstructured":"van der Bom JG, Bots ML, Haverkate F, et al. 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