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This study examined the idea of repurposing an already FDA-approved drug for a new indication\u2014inducing collaterals to remodel to larger diameters after acute stroke. We tested cilostazol, an agent whose molecular mechanism of action suggested such a capability. Importantly, cilostazol is currently used to reduce the incidence of recurrent stroke and transient ischemic attack. In mice with abundant collaterals at baseline, 7-day administration of cilostazol at the dose used clinically beginning 2\u2009h after obstruction of the MCA, boosted collateral growth, that is, anatomic lumen diameter, such that the increase in relative collateral flow post-stroke was augmented by 31% (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.004) 48\u2009h after occlusion. The effect was stronger in mice with poor collaterals, 275% (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.018), in association with a significant decrease in infarct volume and improved functional outcome. Moreover, when combined with an experimental drug that acts by a complimentary mechanism vis-a-vis cilostazol, mice with poor collaterals experienced an additive 261% (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.007) additional increase 7\u2009days post-occlusion. Cilostazol\u2019s augmentation of remodeling extended to mice with advanced age or diabetes. This study provides a basis for further pre-clinical as well as clinical investigation.\n                  <\/jats:p>","DOI":"10.1177\/0271678x251409612","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:30:46Z","timestamp":1768566646000},"page":"1070-1084","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cilostazol increases collateral remodeling and reduces the severity of ischemic stroke"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4625-1916","authenticated-orcid":false,"given":"Hua","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chieh","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0377-6993","authenticated-orcid":false,"given":"James E","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"Curriculum in Neurobiology, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020418"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","DOI":"10.1161\/STR.0000000000000211","article-title":"Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"50","author":"Powers WJ","year":"2019","unstructured":"Powers WJ, Rabinstein AA, Ackerson T, et al. 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