{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:55:17Z","timestamp":1790225717261,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:00:00Z","timestamp":1384387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81202974"],"award-info":[{"award-number":["81202974"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation of the Jiangsu Province of China","award":["BK2011625"],"award-info":[{"award-number":["BK2011625"]}]},{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University","award":["JKGQ201108"],"award-info":[{"award-number":["JKGQ201108"]}]},{"name":"Qing Lan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The blood\u2013brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6\u00a0h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra\u2010performance liquid chromatograph combined with a hybrid quadrupole time\u2010of\u2010flight mass spectrometer (UPLC\u2010MS\/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1\u00a0\u03bcM PAF for 1\u00a0h significantly increased monolayer permeability to <jats:sup>125<\/jats:sup>I\u2010albumin, which recovered 1\u00a0h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1\u00a0h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule\u20101, matrix\u2010metalloproteinase\u20109 and P\u2010glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12507-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain.<\/jats:p>","DOI":"10.1111\/jnc.12507","type":"journal-article","created":{"date-parts":[[2013,10,24]],"date-time":"2013-10-24T16:52:08Z","timestamp":1382633528000},"page":"662-671","source":"Crossref","is-referenced-by-count":27,"title":["Platelet activating factor induces transient blood\u2010brain barrier opening to facilitate edaravone penetration into the brain"],"prefix":"10.1111","volume":"128","author":[{"given":"Weirong","family":"Fang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines Department of Physiology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines Department of Physiology China Pharmaceutical University Nanjing 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