{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:03:41Z","timestamp":1789715021613,"version":"4.0.1"},"reference-count":123,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Ischemic stroke is a leading cause of death and long\u2010term disability worldwide. Recanalization therapies, including thrombolysis and mechanical thrombectomy, restore blood flow, yet many patients experience poor outcomes, a phenomenon known as futile recanalization. Given the short therapeutic window for ischemic stroke, identifying early biomarkers to guide targeted interventions and improve outcomes is critical.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Using a murine middle cerebral occlusion model that mimics a large vessel occlusion with recanalization, a comprehensive microarray analysis from blood samples collected immediately and 3\u2009hours after recanalization (N=44) was performed. Differentially expressed genes, enrichment pathways, immune cell proportions, enriched cell markers, predicted micro\u2010RNAs, and transcription factors were identified using RStudio. Findings in mice were validated with rat middle cerebral artery occlusion (GSE21136) and patients with stroke (GSE16561) data sets to confirm transcriptional changes in peripheral blood postrecanalization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      <jats:italic toggle=\"no\">Il1r2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">Cd55<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">Mmp8<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">Cd14<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"no\">Cd69<\/jats:italic>\n                      were early biomarkers poststroke and postrecanalization. Cross\u2010validation revealed\n                      <jats:italic toggle=\"no\">Vcan<\/jats:italic>\n                      as a differentially expressed gene conserved across species, making it a novel ischemic marker detected as early as 3\u2009hours postrecanalization (4\u2009hours after middle cerebral artery occlusion) in mice, 24\u2009hours after recanalization in rats (middle cerebral artery occlusion\u2010thrombectomy), and within 24\u2009hours from onset in humans receiving recombinant tissue plasminogen activator\u2010thrombolysis. CIBERSORTx and ImmuCellAI\u2010mouse deconvolution showed neutrophil elevation postrecanalization. Leukocyte and neutrophil activation pathways were enriched early after stroke in mice and humans, with stronger upregulation in the female sex. Several regulatory micro\u2010RNAs were identified, and Nuclear Factor Erythroid 4 (NFE4)\u00a0and Metal Regulatory Transcription Factor 1 (MTF1) emerged as key transcription factors. A coregulatory network underlying neutrophil activity was constructed, highlighting its central role in early responses to ischemia and recanalization, which was enriched in the female sex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We identified novel early genomic markers for ischemia and recanalization, including the conserved marker\n                      <jats:italic toggle=\"no\">Vcan<\/jats:italic>\n                      , and highlighted age\u2010 and sex\u2010specific immune responses. Mapping a neutrophil\u2010centered coregulatory network provides mechanistic insight into futile recanalization and supports the development of targeted therapies to improve clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.043522","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:22:51Z","timestamp":1774430571000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Early Transcriptional Changes in Neutrophil\u2010Mediated Processes Following Recanalization After Ischemic Stroke"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-0565","authenticated-orcid":false,"given":"Truong An","family":"Bui","sequence":"first","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]},{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglie","family":"Ma","sequence":"additional","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-0820","authenticated-orcid":false,"given":"Glen C.","family":"Jickling","sequence":"additional","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]},{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8574-4855","authenticated-orcid":false,"given":"Ian R.","family":"Winship","sequence":"additional","affiliation":[{"name":"University of Alberta","place":["Edmonton, Canada"]},{"name":"University of Alberta","place":["Edmonton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00933-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000485"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.11.005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00252-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.028910"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.037117"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.542894"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12126"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2011.11928729"},{"key":"e_1_3_2_11_2","first-page":"480","article-title":"Current endovascular treatment of acute ischemic stroke","volume":"117","author":"Bhatia K","year":"2020","unstructured":"Bhatia K, Bhagavan S, Bains N, et\u00a0al. 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