{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:11:54Z","timestamp":1790082714596,"version":"4.0.1"},"reference-count":187,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["K08NS121597-01A1"],"award-info":[{"award-number":["K08NS121597-01A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stony Brook University Research Foundation","award":["K08NS121597-01A1"],"award-info":[{"award-number":["K08NS121597-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Ischemic stroke is a highly morbid disease, with over 50% of large vessel stroke (middle cerebral artery or internal carotid artery terminus occlusion) patients suffering disability despite maximal acute reperfusion therapy with thrombolysis and thrombectomy. The discovery of the ischemic penumbra in the 1980s laid the foundation for a salvageable territory in ischemic stroke. Since then, the concept of neuroprotection has been a focus of post-stroke care to (1) minimize the conversion from penumbra to core irreversible infarct, (2) limit secondary damage from ischemia-reperfusion injury, inflammation, and excitotoxicity and (3) to encourage tissue repair. However, despite multiple studies, the preclinical\u2013clinical research enterprise has not yet created an agent that mitigates post-stroke outcomes beyond thrombolysis and mechanical clot retrieval. These translational gaps have not deterred the scientific community as agents are under continuous investigation. The NIH has recently promoted the concept of cerebroprotection to consider the whole brain post-stroke rather than just the neurons. This review will briefly outline the translational science of past, current, and emerging breakthroughs in cerebroprotection and use of these foundational ideas to develop a novel paradigm for optimizing stroke outcomes.<\/jats:p>","DOI":"10.3390\/jcm12216715","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T11:39:04Z","timestamp":1698147544000},"page":"6715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Evolving Clinical\u2013Translational Investigations of Cerebroprotection in Ischemic Stroke"],"prefix":"10.3390","volume":"12","author":[{"given":"Yinghui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel E.","family":"Schappell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"},{"name":"Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Polizu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"DiPersio","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0022-1770","authenticated-orcid":false,"given":"Stella E.","family":"Tsirka","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-8565","authenticated-orcid":false,"given":"Marc W.","family":"Halterman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Nadkarni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794-8651, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1161\/STR.0b013e318296aeca","article-title":"An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"44","author":"Sacco","year":"2013","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"20","author":"Feigin","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(1995). 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