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Although rodent models are widely utilized for ischemic stroke research, their limited translational success has driven the pursuit of alternative experimental systems. This review underscores the growing significance of non\u2010mammalian models, particularly\n                    <jats:italic>zebrafish<\/jats:italic>\n                    and\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    <\/jats:styled-content>\n                    , in advancing ischemic stroke research. Zebrafish offer notable advantages, including high genetic homology with humans, optical transparency, a pronounced capacity for neural regeneration, in\u00a0vivo live real\u2010time imaging, and behavioral analyses. Photothrombotic and systemic hypoxia paradigms in zebrafish enable detailed investigation of neurovascular injury and recovery processes.\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , characterized by a rapid life cycle and sophisticated genetic toolkit, serves as a valuable model for elucidating hypoxia\u2010induced neuronal damage and stroke\u2010related comorbidities such as sleep disturbances. These models are cost\u2010efficient, ethically advantageous, and well\u2010suited for high\u2010throughput applications. Despite inherent anatomical and physiological disparities, non\u2010mammalian systems provide critical complementary insights into stroke pathogenesis and therapeutic innovation, reinforcing their integration into multi\u2010model research frameworks.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70112","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T04:26:12Z","timestamp":1768969572000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non\u2010Mammalian Models in Ischemic Stroke Research: Advances, Applications, and Translational Potential"],"prefix":"10.1002","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-6495","authenticated-orcid":false,"given":"Takamasa","family":"Mizoguchi","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Science Chiba University  Chiba 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