{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:34:30Z","timestamp":1790357670941,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Fibrotic scars composed of a dense extracellular matrix are the major obstacles for axonal regeneration. Previous studies have reported that antitumor drugs promote neurofunctional recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the effects of 5\u2010fluorouracil (5\u2010FU), a classical antitumor drug with a high therapeutic index, on fibrotic scar formation, axonal regeneration, and functional recovery after spinal cord injury (SCI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>5\u2010FU administration after hemisection SCI improved hind limb sensorimotor function of the ipsilateral hind paws. 5\u2010FU application also significantly reduced the fibrotic scar formation labeled with aggrecan and fibronectin\u2010positive components, Iba1<jats:sup>+<\/jats:sup>\/CD11b<jats:sup>+<\/jats:sup> macrophages\/microglia, vimentin, chondroitin sulfate proteoglycan 4 (NG2\/CSPG4), and platelet\u2010derived growth factor receptor beta (PDGFR\u03b2)<jats:sup>+<\/jats:sup> pericytes. Moreover, 5\u2010FU treatment promoted stromal cells apoptosis and inhibited fibroblast proliferation and migration by abrogating the polarity of these cells and reducing matrix metalloproteinase 9 expression and promoted axonal growth of spinal neurons via the neuron\u2010specific protein doublecortin\u2010like kinase 1 (DCLK1). Therefore, 5\u2010FU administration impedes the formation of fibrotic scars and promotes axonal regeneration to further restore sensorimotor function after SCI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13930","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T05:40:32Z","timestamp":1659505232000},"page":"2011-2023","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["5\u2010Fluorouracil reduces the fibrotic scar via inhibiting matrix metalloproteinase 9 and stabilizing microtubules after spinal cord injury"],"prefix":"10.1111","volume":"28","author":[{"given":"Yang","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Neurological Disease, West China Hospital, Sichuan University &amp; The Research Units of West China Chinese Academy of Medical Sciences  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, 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