{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T17:30:57Z","timestamp":1778175057151,"version":"3.51.4"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T00:00:00Z","timestamp":1647302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["332652"],"award-info":[{"award-number":["332652"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To date, stroke remains one of the leading causes of death and disability worldwide. Nearly three-quarters of all strokes occur in the elderly (&amp;gt;65 years old), and a vast majority of these individuals develop debilitating cognitive impairments that can later progress into dementia. Currently, there are no therapies capable of reversing the cognitive complications which arise following a stroke. Instead, current treatment options focus on preventing secondary injuries, as opposed to improving functional recovery.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We reconstituted aged (20-month old) mice with Sca-1+ bone marrow (BM) hematopoietic stem cells isolated from aged or young (2-month old) EGFP+ donor mice. Three months later the chimeric aged mice underwent cerebral ischemia\/reperfusion by bilateral common carotid artery occlusion (BCCAO), after which cognitive function was evaluated. Immunohistochemical analysis was performed to evaluate host and recipient cells in the brain following BCCAO.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Young Sca-1+ cells migrate to the aged brain and give rise to beneficial microglial-like cells that ameliorate stroke-induced loss of cognitive function on tasks targeting the hippocampus and cerebellum. We also found that young Sca-1+ cell-derived microglial-like cells possess neuroprotective properties as they do not undergo microgliosis upon migrating to the ischemic hippocampus, whereas the cells originating from old Sca-1+ cells proliferate extensively and skew toward a pro-inflammatory phenotype following injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides a proof-of-principle demonstrating that young BM Sca-1+ cells play a pivotal role in reversing stroke-induced cognitive impairments and protect the aged brain against secondary injury by attenuating the host cell response to injury.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/stmcls\/sxac019","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T20:10:44Z","timestamp":1646943044000},"page":"564-576","source":"Crossref","is-referenced-by-count":10,"title":["Stroke-Induced Neurological Dysfunction in Aged Mice Is Attenuated by Preconditioning with Young Sca-1+ Stem Cells"],"prefix":"10.1093","volume":"40","author":[{"given":"Lukasz","family":"Wlodarek","sequence":"first","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network , Toronto, ON , Canada"},{"name":"Faculty of Medicine, Department weof Physiology, University of Toronto , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal J","family":"Alibhai","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-060X","authenticated-orcid":false,"given":"Ren-Ke","family":"Li","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network , Toronto, ON , Canada"},{"name":"Faculty of Medicine, Department weof Physiology, University of Toronto , Toronto, ON , Canada"},{"name":"Division of Cardiac Surgery, Department of Surgery, University of Toronto , Toronto, ON , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,3,15]]},"reference":[{"key":"2022062217364798100_CIT0001","first-page":"2000","volume-title":"Global Health Estimates 2016: Deaths by Cause, Age, Sex by Country and by Region","author":"Organisation WH.","year":"2016"},{"issue":"12","key":"2022062217364798100_CIT0002","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","article-title":"Heart disease and stroke statistics-2018 update: a report from the American Heart Association.","volume":"137","author":"Benjamin","year":"2018","journal-title":"Circulation."},{"key":"2022062217364798100_CIT0003","first-page":"11","volume-title":"Global Health and Aging 2011","author":"Organisation. 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