{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:42:43Z","timestamp":1774316563830,"version":"3.50.1"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Thrombolysis and endovascular thrombectomy are the primary treatment for ischemic stroke. However, due to the limited time window and the occurrence of adverse effects, only a small number of patients can genuinely benefit from recanalization. Intraarterial injection of rtPA (recombinant tissue plasminogen activator) based on arterial thrombectomy could improve the prognosis of patients with acute ischemic stroke, but it could not reduce the incidence of recanalization\u2010related adverse effects. Recently, selective brain hypothermia has been shown to offer neuroprotection against stroke. To enhance the recanalization rate of ischemic stroke and reduce the adverse effects such as tiny thrombosis, brain edema, and hemorrhage, we described for the first time a combined approach of hypothermia and thrombolysis via intraarterial hypothermic rtPA.<\/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\">We initially established the optimal regimen of hypothermic rtPA in adult rats subjected to middle cerebral artery occlusion. Subsequently, we explored the mechanism of action mediating hypothermic rtPA by probing reduction of brain tissue temperature, attenuation of blood\u2013brain barrier damage, and sequestration of inflammation coupled with untargeted metabolomics. Hypothermic rtPA improved neurological scores and reduced infarct volume, while limiting hemorrhagic transformation in middle cerebral artery occlusion rats. These therapeutic outcomes of hypothermic rtPA were accompanied by reduced brain temperature, glucose metabolism, and blood\u2013brain barrier damage. A unique metabolomic profile emerged in hypothermic rtPA\u2010treated middle cerebral artery occlusion rats characterized by downregulated markers for energy metabolism and inflammation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The innovative use of hypothermic rtPA enhances their combined, as opposed to stand\u2010alone, neuroprotective effects, while reducing hemorrhagic transformation in ischemic stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.029817","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T09:22:11Z","timestamp":1693560131000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Cold Case of Thrombolysis: Cold Recombinant Tissue Plasminogen Activator Confers Enhanced Neuroprotection in Experimental Stroke"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5830-1207","authenticated-orcid":false,"given":"Yuyou","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziping","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenghong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyuan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4308-0659","authenticated-orcid":false,"given":"Lingzi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-8974","authenticated-orcid":false,"given":"Yumin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of Cerebrovascular Diseases Research Xuanwu Hospital of Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases Beijing China"},{"name":"Beijing Institute for Brain Disorders Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-9782","authenticated-orcid":false,"given":"Cesario","family":"Borlongan","sequence":"additional","affiliation":[{"name":"University of South Florida Tampa FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine, Institute of 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