{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T04:23:14Z","timestamp":1793766194280,"version":"4.6.1"},"reference-count":37,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471330"],"award-info":[{"award-number":["82471330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Aging has a profound impact on the pathophysiology of ischemic stroke and the effectiveness of therapeutic interventions. This study aims to evaluate the therapeutic efficacy of programmed death\u2010ligand 1 (PD\u2010L1) monoclonal antibody (mAb) in modulating immune responses and neurovascular repair following ischemic stroke, with a focus on age\u2010dependent differences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Young and aged mice were subjected to middle cerebral artery occlusion (MCAO) followed by PD\u2010L1 mAb treatment. RNA sequencing, immunofluorescence, and molecular analyses were employed to assess immune modulation, blood\u2013brain barrier (BBB) integrity, and functional recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA sequencing revealed significant differential gene expression in ischemic brain tissues, with CD274 (PD\u2010L1) prominently upregulated among immune checkpoint\u2010related genes in young mice. Immunofluorescence confirmed PD\u2010L1 expression in microglia\/macrophages, with significantly higher upregulation in young mice. PD\u2010L1 mAb treatment showed superior efficacy in young mice, significantly reducing infarct volume, enhancing neurological recovery, and preserving BBB integrity through greater upregulation of tight junction proteins such as ZO\u20101, Claudin\u20105, and Occludin compared to aged mice. It also more effectively reduced neuroinflammation, apoptosis, and pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2), eliciting stronger spleen responses in young mice. These findings underscore the age\u2010dependent advantages of PD\u2010L1\u2010targeted therapies for ischemic stroke recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PD\u2010L1 plays a critical role in ischemic stroke recovery, with PD\u2010L1 mAb treatment demonstrating age\u2010dependent therapeutic efficacy by enhancing BBB integrity, reducing neuroinflammation and apoptosis, and modulating peripheral immune responses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70523","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T05:46:21Z","timestamp":1753335981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Targeting <scp>PD<\/scp>\u2010<scp>L1<\/scp> for Ischemic Stroke Recovery: Age\u2010Dependent Modulation of Immune and <scp>BBB<\/scp> Pathways"],"prefix":"10.1111","volume":"31","author":[{"given":"Hang","family":"Hang","sequence":"first","affiliation":[{"name":"Emergency Department the Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou China"},{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Joint Innovation Center for Brain Disorders Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Joint Innovation Center for Brain Disorders Capital Medical University  Beijing China"},{"name":"College of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine  Kunming 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