Cilostazol increases collateral remodeling and reduces the severity of ischemic stroke
Year: 2026
Type: article
Abstract: The need to identify therapies capable of increasing collateral blood flow after stroke has recently come into focus. This study examined the idea of repurposing an already FDA-approved drug for a new indication—inducing 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 h 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% ( p = 0.004) 48 h after occlusion. The effect was stronger in mice with poor collaterals, 275% ( p = 0.018), 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% ( p = 0.007) additional increase 7 days post-occlusion. Cilostazol’s 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.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Funders: Institut de recherche, Centre universitaire de santé McGill, American Heart Association, Leona M. and Harry B. Helmsley Charitable Trust, Fondation Brain Canada, University of Texas at Arlington, Japan Agency for Medical Research and Development, Aarne Koskelon Säätiö, Wellcome Trust, Royal College of General Practitioners, Chongqing Postdoctoral Science Foundation, Health Commission of Hebei Province, VitreoRetinal Surgery Foundation, Swedish Foundation for MS Research, Réseau de cancérologie Rossy, Biodiversa+, Vellore Institute of Technology, Chennai, Beijing Health Promotion Association, Royal Society, European Commission, University of Glasgow, European Cooperation in Science and Technology, Hermon Slade Foundation, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Fundação de Amparo à Pesquisa do Estado de São Paulo, National Natural Science Foundation of China, Vienna Science and Technology Fund, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Austrian Science Fund, China Postdoctoral Science Foundation, Ministero della Salute, Natural Science Foundation of Fujian Province, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Javna Agencija za Raziskovalno Dejavnost RS, Polska Akademia Nauk, Narodowym Centrum Nauki, Technische Universität München, Hôpitaux Universitaires de Genève, Université de Genève, Natural Science Foundation of Shandong Province, Stiftelsen för Åbo Akademi, Instrumentariumin Tiedesäätiö, Paavo Nurmen Säätiö, Fondazione Grigioni per il Morbo di Parkinson, Marcus och Amalia Wallenbergs minnesfond, Fundamental Research Funds for the Key Research Program of Chongqing Science and Technology Commission, Max Planck Institute for Nuclear Physics, Hunan Provincial People's Hospital, National Science and Technology Major Project, Science and Technology Program of Hunan Province, Fonds de recherche du Québec, Ministero dell'Università e della Ricerca, National Institutes of Health, GE Healthcare, Agricultural Research Service, Alzheimer Society Research Program, Bayer, United Kingdom, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Biotechnology and Biological Sciences Research Council, Australian Research Council, Japan Society for the Promotion of Science, Instituto Nazionale di Fisica Nucleare, Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Science and Technology Innovation Plan Of Shanghai Science and Technology Commission, NIHR Nottingham Biomedical Research Centre, Research Institute, University of Bucharest, Cancer Research UK Cambridge Institute, University of Cambridge, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Institute of Dental and Craniofacial Research, National Marine Fisheries Service, H2020 European Research Council, Military Operational Medicine Research Program, Fondation Mirella et Lino Saputo
Award: G603485939
OpenAlex ID: W7124441104