{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:39:48Z","timestamp":1789717188574,"version":"4.0.1"},"reference-count":160,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,7,15]]},"abstract":"<jats:sec id=\"jah311072-sec-0001\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Stroke is a leading cause of death, with patients often experiencing significant disability. Stroke is classified as ischemic, caused by the occlusion of a blood vessel leading to reduction in cerebral blood flow, or hemorrhagic, resulting from the rupture of a vessel that causes bleeding into the brain. Transforming growth factor \u03b21 (TGF\u2010\u03b21), a pleiotropic cytokine, has been investigated in stroke due to its diverse effects on proliferation, extracellular matrix deposition, and inflammation. This systematic review examined the role of TGF\u2010\u03b21 in preclinical studies of ischemic and hemorrhagic stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah311072-sec-0002\" xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">A search of PubMed, Web of Science, and Scopus databases identified animal studies examining TGF\u2010\u03b21 signaling as an outcome or intervention. A total of 89 studies were included: 68 on ischemic stroke and 21 on hemorrhagic stroke. Studies were assessed for bias following the SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation) guidelines, followed by extraction of methodology and the role of TGF\u2010\u03b21.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah311072-sec-0003\" xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Compliance with SYRCLE guidelines was found to be low, and the methodological approaches to stroke models were variable. A range of interventions were shown to modify TGF\u2010\u03b21 expression or signaling, with exogenous TGF\u2010\u03b21 improving outcomes in all ischemic stroke studies. TGF\u2010\u03b21 was found to play a protective role in 76% of ischemic stroke studies but was only protective in 33% of hemorrhagic stroke studies, with likely involvement in fibrosis development in the latter.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec id=\"jah311072-sec-0004\" xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our findings suggest a marked difference in TGF\u2010\u03b21 function between these types of stroke, and it is hypothesized that blood cytotoxicity following hemorrhagic stroke may generate more sustained TGF\u2010\u03b21 expression than that seen in ischemic stroke. This may lead to TGF\u2010\u03b21\u2013mediated fibrosis and hydrocephalus, as opposed to the neuroprotective role played by the same molecule following ischemic stroke. These findings highlight the possible clinical utility of exogenous TGF\u2010\u03b21 therapies after ischemic stroke, and TGF\u2010\u03b21 inhibitors after hemorrhagic stroke, to reduce morbidity and disability caused by these events.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.037890","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T09:05:32Z","timestamp":1751360732000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Systematic Review of the Differential Effects of TGF\u2010\u03b21 in Ischemic and Hemorrhagic Preclinical Stroke Models"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1609-6054","authenticated-orcid":false,"given":"Benjamin J.","family":"Hewitt","sequence":"first","affiliation":[{"name":"University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8261","authenticated-orcid":false,"given":"Myah","family":"Ali","sequence":"additional","affiliation":[{"name":"University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6143-2306","authenticated-orcid":false,"given":"Jessica","family":"Hubbard","sequence":"additional","affiliation":[{"name":"University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8431-7029","authenticated-orcid":false,"given":"Lisa J.","family":"Hill","sequence":"additional","affiliation":[{"name":"University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4564-0282","authenticated-orcid":false,"given":"Hannah","family":"Botfield","sequence":"additional","affiliation":[{"name":"University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","first-page":"1","article-title":"Deaths: leading causes for 2018","volume":"70","author":"Heron M","year":"2021","unstructured":"Heron M. 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