{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T02:00:34Z","timestamp":1772503234157,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RF1NS131110"],"award-info":[{"award-number":["RF1NS131110"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG063808"],"award-info":[{"award-number":["R01AG063808"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01RX003224"],"award-info":[{"award-number":["I01RX003224"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32AG058503-01A1"],"award-info":[{"award-number":["T32AG058503-01A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq Transatlantic Network of Excellence","doi-asserted-by":"publisher","award":["19CVD01"],"award-info":[{"award-number":["19CVD01"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipid debris generated after ischemic stroke overwhelms myeloid cells, leading to foam cell-like dysfunction and chronic neuroinflammation. 2-hydroxypropyl-\u03b2-cyclodextrin (HP\u03b2CD), a cholesterol-mobilizing agent, has been shown to improve recovery and reduce chronic inflammation after stroke by enhancing lipid processing and cholesterol efflux in infarcts. To identify plasma biomarkers of HP\u03b2CD activity and gain mechanistic insight into lipid pathway modulation, aged (21-month-old) male mice underwent the distal middle cerebral artery occlusion + hypoxia (DH) model of stroke and received 2 g\/kg HP\u03b2CD twice daily beginning 1 d after stroke. Plasma metabolomic and lipidomic profiling was performed 4 d after stroke using untargeted (Global Discovery) and targeted (Complex Lipid, Oxysterols, and Lipid Mediators of Inflammation) panels. Acute neuroprotection was assessed by magnetic resonance imaging (MRI) quantification of infarct, ventricle, and hippocampus volumes 2 d after stroke and by plasma neurofilament light (NfL) levels 4 d after stroke. HP\u03b2CD treatment did not provide acute neuroprotection; however, HP\u03b2CD did induce distinct plasma metabolomic and lipidomic signatures, including decreases in sphingolipids, cholesterol, long-chain fatty acids, 4\u03b2-hydroxycholesterol, 7-dehydrocholesterol, and 8-dehydrocholesterol and increases in 27-hydroxycholesterol and 7\u03b1-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA), consistent with enhanced cholesterol efflux and metabolism. Pro-inflammatory oxylipins were also suppressed by HP\u03b2CD treatment. These results support the role of HP\u03b2CD in promoting lipid debris clearance and suppressing inflammatory lipid pathways after stroke and, together with prior studies demonstrating improved long-term recovery, highlight HP\u03b2CD as a biomarker-supported therapeutic candidate for stroke recovery.<\/jats:p>","DOI":"10.3390\/ijms262210814","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:14:45Z","timestamp":1762506885000},"page":"10814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma Biomarker Profiling of 2-Hydroxypropyl-\u03b2-Cyclodextrin (HP\u03b2CD) Treatment in an Aged Mouse Model of Ischemic Stroke"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8463-0282","authenticated-orcid":false,"given":"Danielle A.","family":"Becktel","sequence":"first","affiliation":[{"name":"Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer B.","family":"Frye","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth H.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick G.","family":"Schnellmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Coit Center for Longevity and Neurotherapeutics, R. Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ 85724, USA"},{"name":"BIO5 Institute, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2788-7038","authenticated-orcid":false,"given":"Kristian P.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"},{"name":"BIO5 Institute, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Arizona Center on Aging, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Psychology, College of Science, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Neurosurgery, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1479-5876-7-97","article-title":"Inflammatory mechanisms in ischemic stroke: Therapeutic approaches","volume":"7","author":"Lakhan","year":"2009","journal-title":"J. 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