{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:54:27Z","timestamp":1790121267149,"version":"4.0.1"},"reference-count":9,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatology"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> Neonatal hypoxic-ischemic brain injury (HIBI) results in significant morbidity and mortality despite current available therapies. Seeking a potential supplemental therapy for HIBI, we investigated the neuroprotective effects of extracellular vesicles derived from neural stem cells (NSC-EVs) and hypoxia-preconditioned brain cells (brain-EVs). <b><i>Methods:<\/i><\/b> HIBI was induced in postnatal day 9 mice by carotid ligation followed by hypoxia. Following injury, NSC-EVs, brain-EVs, or saline were administered intranasally. Brains were assessed for infarct size, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and caspase-3 expression. Additionally, brain-EV microRNA (miRNA) contents were analyzed by miRNA sequencing. <b><i>Results:<\/i><\/b> Both EV treated groups showed decreased infarct size (brain-EVs <i>p<\/i> = 0.004 and NSC-EVs <i>p<\/i> = 0.052), and although NSC-EV administration resulted in significantly fewer TUNEL+ cells (<i>p<\/i> = 0.0098), there was no change in caspase-3 expression after NSC-EV administration, suggesting a caspase-3-independent mechanism. Brain-EVs resulted in a nonsignificant decrease in TUNEL+ cells (<i>p<\/i> = 0.167) but significant decreases in caspase expression (cleaved <i>p<\/i> = 0.015 and intact <i>p<\/i> = 0.026). Brain-EVs consistently expressed several miRNAs, including two which have been shown to be downregulated after HIBI: miR-342-3p and miR-330-3p. <b><i>Conclusion:<\/i><\/b> Understanding the regenerative effects and contents of NSC-EVs and brain-EVs could allow for the development of targeted EV-based therapies that could reduce morbidity and mortality for neonates affected by HIBI. <\/jats:p>","DOI":"10.1159\/000522644","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T06:50:03Z","timestamp":1648450203000},"page":"345-353","source":"Crossref","is-referenced-by-count":27,"title":["Intranasal Administration of Extracellular Vesicles Mitigates Apoptosis in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury"],"prefix":"10.1159","volume":"119","author":[{"given":"Abby","family":"Lawson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-2678","authenticated-orcid":false,"given":"Eric S.","family":"Peeples","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2010.05.010"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189895"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0250-9"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0240-6"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6728-5_10"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080855"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10372"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101207"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1113\/EP088708"}],"container-title":["Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/522644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/522644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:52:57Z","timestamp":1745423577000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000522644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":9,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,5,17]]},"published-print":{"date-parts":[[2022,5,24]]}},"URL":"https:\/\/doi.org\/10.1159\/000522644","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.19419137","asserted-by":"subject"}]},"ISSN":["1661-7800","1661-7819"],"issn-type":[{"value":"1661-7800","type":"print"},{"value":"1661-7819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}