{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:35:47Z","timestamp":1782977747895,"version":"3.54.5"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Plasminogen activator inhibitor-I (PAI-1), a \u224850-kDa serine protease inhibitor, markedly reduces the extravascular toxicity of tissue-type plasminogen activator in experimental hypoxic\u2013ischemic (HI) brain injury of newborns. However, the current treatment with PAI-1 requires intracerebroventricle injection to cross the blood\u2013brain barrier, which is an invasive procedure of limited clinical potential. Thus, we tested whether intranasal administration of PAI-1 can bypass blood\u2013brain barrier and mitigate neonatal HI brain injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Rat pups were subjected to HI, with or without lipopolysaccharide pre-exposure, followed by intranasal delivery of a stable-mutant form of PAI-1 (CPAI).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Immunoblotting showed that CPAI sequentially entered the olfactory bulbs and cerebral cortex after intranasal delivery and reduced \u224875% of brain atrophy in HI or lipopolysaccharide-sensitized HI injury. Mechanistically, CPAI attenuated HI-induced plasminogen activators and lipopolysaccharide\/HI-induced nuclear factor-\u03baB signaling, neuroinflammation, and blood\u2013brain barrier permeability.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Intranasal delivery of CPAI is an effective treatment of experimental HI brain injury of newborns. Clinical application of this experimental therapy merits further investigation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.113.001233","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T17:44:25Z","timestamp":1374687865000},"page":"2623-2627","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Taming Neonatal Hypoxic\u2013Ischemic Brain Injury by Intranasal Delivery of Plasminogen Activator Inhibitor-1"],"prefix":"10.1161","volume":"44","author":[{"given":"Dianer","family":"Yang","sequence":"first","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Yo","family":"Sun","sequence":"additional","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Lin","sequence":"additional","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Baumann","sequence":"additional","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Warnock","sequence":"additional","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Kuan","sequence":"additional","affiliation":[{"name":"From the Division of Developmental Biology, Department of Pediatrics, Cincinnati\u2019s Children\u2019s Hospital Medical Center, Cincinnati, OH (D.Y., Y.-Y.S., J.M.B., C.-Y.K.); Division of Neurology, Department of Pediatrics, The Center for Neurodegenerative Disease (CND), The Emory University School of Medicine, Atlanta, GA (D.Y., Y.-Y.S., X.L., C.-Y.K.); and Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (M.W., D.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000137868.50767.E8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000143219.16695.af"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1117-09.2009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs115"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1002\/j.1460-2075.1995.tb07299.x","article-title":"Molecular evolution of plasminogen activator inhibitor-1 functional stability.","volume":"14","author":"Berkenpas MB","year":"1995","unstructured":"Berkenpas MB, Lawrence DA, Ginsburg D. 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EMBO J. 1995;14:2969\u20132977.","journal-title":"EMBO J"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000163513.03619.8D"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21924"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.233"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.01.015"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.09.029"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.08.024"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20241"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.113.001233","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:00:25Z","timestamp":1715608825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.113.001233"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9]]},"references-count":12,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1161\/STROKEAHA.113.001233"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.113.001233","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,9]]},"assertion":[{"value":"2013-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}