{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:53:59Z","timestamp":1791910439141,"version":"4.3.4"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Irisin, a myokine cleaved from its precursor FNDC5 (fibronectin type III domain-containing protein 5) following exercise or low-frequency whole-body vibration, regulates energy metabolism and insulin sensitivity. This study examines irisin\u2019s therapeutic potential in stroke in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Adult Sprague-Dawley rats of both sexes underwent transient middle cerebral artery occlusion (90 minutes) or sham surgery. After 4.5 hours, they were randomized to receive saline or irisin treatment (0.1, 0.2, and 0.8 \u03bcg\/g body weight). Infarct volume was quantified 1 day after transient middle cerebral artery occlusion using 2,3,5-triphenyltetrazolium chloride staining. In a subsequent study, reproductively senescent female rats received either saline or 0.2 \u03bcg\/g body weight irisin at 4.5 hours post-transient middle cerebral artery occlusion, followed by weekly treatments for a month. Sensorimotor and cognitive functions were assessed using the cylinder test and Morris water maze. Ipsilateral cortical tissue was collected from a subset of the reproductive senescence rats following 2 weeks of treatment for RNA sequencing and real-time quantitative polymerase chain reaction analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Irisin (0.2 \u03bcg\/g) significantly reduced infarct volume by 50% in females and 36% in males compared with their respective saline groups. In reproductive senescence females, irisin treatment for a month improved contralateral limb use by day 7 and enhanced spatial learning in the Morris water maze, reducing latency to find the hidden platform on the fourth day of testing (16.5 sec versus saline;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05) and increasing time spent in the target quadrant during the probe trial (9.3 sec versus saline;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05). Irisin therapy significantly altered cortical gene expression, with 332 genes upregulated and 136 downregulated. Gene ontology analysis revealed genes linked to the extracellular matrix were significantly upregulated, which was confirmed by increased expression of the cell-surface integrin \u03b1V\u03b25, known to interact with irisin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Post-transient middle cerebral artery occlusionirisin therapy modulates the transcriptome, enhancing motor and cognitive function while protecting against ischemic brain damage in middle-aged female rats.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.053168","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T10:00:20Z","timestamp":1762336820000},"page":"197-204","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Recombinant Irisin Therapy Alters Brain Transcriptome and Protects Against Ischemic Damage in Middle-Aged Rats"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3423-7503","authenticated-orcid":true,"given":"Shahil H.","family":"Patel","sequence":"first","affiliation":[{"name":"Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL) (S.H.P., I.C.D., A.P.R.), , University of Miami, FL"},{"name":"Department of Neurology (S.H.P., I.C.D., A.P.R.), University of Miami, FL"},{"name":"Neuroscience Graduate Program, Leonard M. Miller School of Medicine, University of Miami, FL (S.H.P., W.D.D., H.M.B., A.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indy Cabeda","family":"Diaz","sequence":"additional","affiliation":[{"name":"Peritz Scheinberg Cerebral Vascular Disease Research Laboratory (CVDRL) (S.H.P., I.C.D., A.P.R.), , University of Miami, FL"},{"name":"Department of Neurology (S.H.P., I.C.D., A.P.R.), University of Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-9186","authenticated-orcid":true,"given":"Zhexuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, FL (Z.Z., W.Z., W.D.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-5785","authenticated-orcid":true,"given":"Weizhao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, FL (Z.Z., W.Z., W.D.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Dalton","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, Leonard M. Miller School of Medicine, University of Miami, FL (S.H.P., W.D.D., H.M.B., A.P.R.)."},{"name":"Department of Neurological Surgery (W.D.D., H.M.B.), University of Miami, FL"},{"name":"The Miami Project to Cure Paralysis, Leonard M. Miller School of Medicine, University of Miami, FL (W.D.D., H.M.B.)"},{"name":"Department of Biomedical Engineering, University of Miami, Coral Gables, FL (Z.Z., W.Z., W.D.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-0973","authenticated-orcid":true,"given":"Helen M.","family":"Bramlett","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, Leonard M. Miller School of Medicine, University of Miami, FL (S.H.P., W.D.D., H.M.B., A.P.R.)."},{"name":"Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL (H.M.B., A.P.R.)."},{"name":"Department of Neurological Surgery (W.D.D., H.M.B.), University of Miami, FL"},{"name":"The Miami Project to Cure Paralysis, Leonard M. 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