{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T01:31:57Z","timestamp":1789867917973,"version":"4.0.1"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["935826"],"award-info":[{"award-number":["935826"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["26BCDA1622703"],"award-info":[{"award-number":["26BCDA1622703"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24TPA1291189"],"award-info":[{"award-number":["24TPA1291189"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"award":["935826"],"award-info":[{"award-number":["935826"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["26BCDA1622703"],"award-info":[{"award-number":["26BCDA1622703"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["24TPA1291189"],"award-info":[{"award-number":["24TPA1291189"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Exosomes (EXs) mediate intercellular communication in the tissue microenvironment. We previously demonstrated that endothelial progenitor cell-derived exosomes (EPC-EXs) from exercised mice protect neurons and cerebral endothelial cells from hypoxia- and hypertension- induced injury ex vivo, suggesting their therapeutic potential in hypertensive ischemic injury. Here, we investigated whether exercise-conditioned EPC-EXs (ET-EPC-EXs) confer protection against acute ischemic injury. Hypertensive transgenic mice were divided into donor and recipient groups. Donor mice underwent treadmill exercise to generate ET-EPC-EXs. Recipient mice was subjected to middle cerebral artery occlusion and received ET-EPC-EXs via tail vein injection (2 \u00d7 108\/100 \u03bcL saline) two hours after stroke onset. Cerebral blood flow (CBF) was assessed, and brains were collected on day two for histological and molecular analyses. Our data showed that ET-EPC-EXs were robustly taken up by cerebral cells, predominantly in the penumbra in the ipsilateral hemisphere. ET-EPC-EXs reduced cell death and microglia activation and restored tight-junction proteins. Moreover, ET-EPC-EX treatment preserved CBF and improved sensorimotor function on day two post-stroke. Mechanistically, ET-EPC-EXs suppressed p38 activation, accompanied by reduced matrix metalloproteinase-3 and cytochrome c levels in the ipsilateral brain. Collectively, these findings demonstrate that EPC-EXs from exercise mice improve sensorimotor functions and confer protection in hypertensive ischemic brain injury, likely through attenuation of neuroinflammation and preservation of vascular integrity via modulation of the p38 signaling.<\/jats:p>","DOI":"10.3390\/life16040623","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:49:44Z","timestamp":1775641784000},"page":"623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise-Conditioned Endothelial Progenitor Cell-Exosomes Preserve Cerebral Blood Flow and Alleviate Acute Ischemic Brain Injury in Hypertensive Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Shuzhen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4466-0127","authenticated-orcid":false,"given":"Smara","family":"Sigdel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3846-8935","authenticated-orcid":false,"given":"Gideon","family":"Udoh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon Xiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1210-7676","authenticated-orcid":false,"given":"Jinju","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1159\/000533737","article-title":"Blood Pressure Variability Is Associated with Infarct Growth in Acute Ischaemic Stroke","volume":"53","author":"Woods","year":"2024","journal-title":"Cerebrovasc. 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