ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated. If you have any questions, please contact Marianne Reed at mreed@ku.edu .

Show simple item record

dc.contributor.authorYan, Jingqi
dc.contributor.authorZhou, Bo
dc.contributor.authorTaheri, Saeid
dc.contributor.authorShi, Honglian
dc.date.accessioned2012-05-07T18:01:01Z
dc.date.available2012-05-07T18:01:01Z
dc.date.issued2011-11-16
dc.identifier.citationYan J, Zhou B, Taheri S, and Shi H. Differential effects of HIF-1 inhibition by YC-1 on the overall outcome and blood brain-barrier damage in a rat model of ischemic stroke. PLoS One 6(11): e27798; 2011. http://dx.doi.org/10.1371/journal.pone.0027798
dc.identifier.urihttp://hdl.handle.net/1808/9285
dc.descriptionThis is the publisher's version, also available from http://dx.doi.org/10.1371/journal.pone.0027798.
dc.description.abstractHypoxia-inducible factor 1 (HIF-1) is a master regulator of cellular adaptation to hypoxia and has been suggested as a potent therapeutic target in cerebral ischemia. Here we show in an ischemic stroke model of rats that inhibiting HIF-1 and its downstream genes by 3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole (YC-1) significantly increases mortality and enlarges infarct volume evaluated by MRI and histological staining. Interestingly, the HIF-1 inhibition remarkably ameliorates ischemia-induced blood-brain barrier (BBB) disruption determined by Evans blue leakage although it does not affect brain edema. The result demonstrates that HIF-1 inhibition has differential effects on ischemic outcomes and BBB permeability. It indicates that HIF-1 may have different functions in different brain cells. Further analyses show that ischemia upregulates HIF-1 and its downstream genes erythropoietin (EPO), vascular endothelial growth factor (VEGF), and glucose transporter (Glut) in neurons and brain endothelial cells and that YC-1 inhibits their expression. We postulate that HIF-1-induced VEGF increases BBB permeability while certain other proteins coded by HIF-1’s downstream genes such as epo and glut provide neuroprotection in an ischemic brain. The results indicate that YC-1 lacks the potential as a cerebral ischemic treatment although it confers certain protection to the cerebral vascular system.
dc.language.isoen
dc.publisherPublic Library of Science
dc.titleDifferential Effects of HIF-1 Inhibition by YC-1 on the Overall Outcome and Blood-Brain Barrier Damage in a Rat Model of Ischemic Stroke
dc.typeArticle
kusw.kuauthorYan, Jingqi
kusw.kuauthorZhou, Bo
kusw.kuauthorShi, Honglian
kusw.kudepartmentPharmacology and Toxicology
kusw.oastatusfullparticipation
dc.identifier.doi10.1371/journal.pone.0027798
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record