{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:17:50Z","timestamp":1778253470103,"version":"3.51.4"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ60458"],"award-info":[{"award-number":["2023JJ60458"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ30367"],"award-info":[{"award-number":["2023JJ30367"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ischemic stroke results in inhibition of axonal regeneration but the roles of fibrinogen (Fg) in neuronal signaling and energy crises in experimental stroke are under-investigated. We explored the mechanism of Fg modulation of axonal regeneration and neuronal energy crisis after cerebral ischemia using a permanent middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons under low glucose-low oxygen. Behavioral tests assessed neurological deficits; immunofluorescence, immunohistochemistry, and Western-blot analyzed Fg and protein levels. Fluo-3\/AM fluorescence measured free Ca2+ and ATP levels were gauged via specific assays and F560nm\/F510nm ratio calculations. Mito-Tracker Green labeled mitochondria and immunoprecipitation studied protein interactions. Our comprehensive study revealed that Fg inhibited axonal regeneration post-MCAO as indicated by reduced GAP43 expression along with elevated free Ca2+, both suggesting an energy crisis. Fg impeded mitochondrial function and mediated impairment through the EGFR\/Ca2+ axis by trans-activating EGFR via integrin \u03b1v\u03b23 interaction. These results indicate that the binding of Fg with integrin \u03b1v\u03b23 leads to the trans-activation of the EGFR\/Ca2+ signaling axis thereby disrupting mitochondrial energy transport and axonal regeneration and exacerbating the detrimental effects of ischemic neuronal injury.<\/jats:p>","DOI":"10.1093\/jnen\/nlae114","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T11:21:50Z","timestamp":1728386510000},"page":"210-222","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms of fibrinogen trans-activation of the EGFR\/Ca2+ signaling axis to regulate mitochondrial transport and energy transfer and inhibit axonal regeneration following cerebral ischemia"],"prefix":"10.1093","volume":"84","author":[{"given":"Shengqiang","family":"Zhou","sequence":"first","affiliation":[{"name":"National TCM Master Liu Zuyi Inheritance Studio, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine) , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Hunan University of Chinese Medicine , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dahua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine) , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate School, Hunan University of Chinese Medicine , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zeng","sequence":"additional","affiliation":[{"name":"Graduate School, Hunan University of Chinese Medicine , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate School, Hunan University of Chinese Medicine , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjuan","family":"Tan","sequence":"additional","affiliation":[{"name":"Graduate School, Hunan University of Chinese Medicine , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo","family":"Mao","sequence":"additional","affiliation":[{"name":"Key Project Office, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine) , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"National TCM Master Liu Zuyi Inheritance Studio, Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine (The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine) , Changsha City, Hunan Province,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"2025022107521359400_nlae114-B1","first-page":"e29","article-title":"Heart disease and stroke statistics\u20142015 update: a report from the American Heart 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