{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:40:21Z","timestamp":1792658421592,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Intravenous thrombolysis (IVT) failure in acute ischemic stroke (AIS) is frequent, but its causes remain elusive. We investigated whether biologically relevant intrathrombus concentrations of tissue plasminogen activator (tPA) were achieved in failed IVT and whether neutrophil extracellular traps (NETs) contributed to this therapeutic failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this monocenter cohort study, 205 thrombi from AIS patients were analyzed. A total of 83 of these thrombi were compared for tPA content and 53 for their susceptibility to ex vivo thrombolysis according to IVT status. An additional subset of 69 AIS thrombi was used to decipher if and how NETs interfere with intrathrombus fibrinolysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thrombi from IVT patients contained twice as much tPA than those from no\u2010IVT patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Plasminogen and tPA in AIS thrombi were associated with fibrin, leukocytes, and NETs. Although ex vivo addition of plasminogen did not cause lysis of either no\u2010IVT or IVT thrombi, combining plasminogen with deoxyribonuclease 1 (DNase 1) helped translate the increased tPA content of IVT thrombi into increased thrombolysis. We further show that DNase 1 enables tPA\u2010 and plasmin\u2010mediated thrombolysis by eliminating fibrinolysis inhibitors from AIS thrombi.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These results indicate that intrathrombus tPA concentrations reached in failed IVT bear a therapeutic potential that is impaired by NETs, which favor intrathrombus retention of fibrinolysis inhibitors and may limit the availability of tPA and plasminogen for fibrinolysis. Our results stress the interest of DNase 1 to enhance the efficacy of current IVT tPA regimens. ANN NEUROL 2026;100:964\u2013978<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78346","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:24:59Z","timestamp":1789478699000},"page":"964-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil Extracellular Traps Block Fibrinolysis in Ischemic Stroke"],"prefix":"10.1002","volume":"100","author":[{"given":"Mialitiana","family":"Solo Nomenjanahary","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 INSERM, Optimisation Th\u00e9rapeutique en Neuropharmacologie OTEN U1144  Paris France"},{"name":"Biological Resource Center and Department of Interventional Neuroradiology Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Philippe","family":"Desilles","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris 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