{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T23:03:36Z","timestamp":1779663816866,"version":"3.53.1"},"reference-count":61,"publisher":"Georg Thieme Verlag KG","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22077016"],"award-info":[{"award-number":["22077016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32370990"],"award-info":[{"award-number":["32370990"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32371312"],"award-info":[{"award-number":["32371312"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82070142"],"award-info":[{"award-number":["82070142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key Research and Development Program of China","award":["2023YFE0118400"],"award-info":[{"award-number":["2023YFE0118400"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"crossref","award":["2023Y4016"],"award-info":[{"award-number":["2023Y4016"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:p>Acute ischemic stroke is a leading cause of global disability and mortality. Current therapies are limited by a narrow 4.5-hour treatment window, high risk of bleeding, frequent reocclusion post-thrombolysis, and poor neuroprotective\/repair capacity.<\/jats:p>\n                  <jats:p>The thrombolytic activity of citPA5 with or without tirofiban was first assessed using in vitro clot lysis assays. Therapeutic efficacy and safety were then evaluated in a murine carotid embolism-induced stroke model. Mice received citPA5 plus tirofiban at 0.5 hours after occlusion. Cerebral blood flow, infarct volume, neurological function, platelet accumulation, microglial activation, and cerebral hemorrhage were assessed.<\/jats:p>\n                  <jats:p>In vitro, tirofiban did not impair citPA5-mediated thrombolysis. In vivo, citPA5 plus tirofiban improved cerebral blood flow recovery to 71.7% at 3 hours and 89.2% at 24 hours, reduced infarct volume to 4.2%, and accelerated neurological recovery, with significant improvement sustained over a 7-day observation period. Immunofluorescence analysis showed modest reduction of platelet accumulation and marked attenuation of CD68+Iba1+ microglial activation, with partial restoration of ramified microglial morphology. No significant cerebral hemorrhage was observed.<\/jats:p>\n                  <jats:p>Combined citPA5 and tirofiban therapy enhances reperfusion, mitigates thrombo-inflammatory injury, and promotes both acute and longer-term neurological recovery in a mouse ischemic stroke model. These findings support this dual thrombolytic\u2013antiplatelet strategy as a potentially safe and effective therapeutic approach for ischemic stroke.<\/jats:p>","DOI":"10.1055\/a-2870-6746","type":"journal-article","created":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T22:30:51Z","timestamp":1779661851000},"source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Thrombolysis\u2013Antiplatelet Therapy of Engineered tPA Variant citPA5 and Tirofiban in a Mouse Stroke Model"],"prefix":"10.1055","author":[{"given":"Honglian","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry, Fuzhou University, Fujian, China","place":["Fuzhou"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiping","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Chemistry, Fuzhou University, Fujian, 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