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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
dc.contributor.author | Yan, Jingqi | |
dc.contributor.author | Zhou, Bo | |
dc.contributor.author | Taheri, Saeid | |
dc.contributor.author | Shi, Honglian | |
dc.date.accessioned | 2012-05-07T18:01:01Z | |
dc.date.available | 2012-05-07T18:01:01Z | |
dc.date.issued | 2011-11-16 | |
dc.identifier.citation | Yan 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.uri | http://hdl.handle.net/1808/9285 | |
dc.description | This is the publisher's version, also available from http://dx.doi.org/10.1371/journal.pone.0027798. | |
dc.description.abstract | Hypoxia-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.iso | en | |
dc.publisher | Public Library of Science | |
dc.title | 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 | |
dc.type | Article | |
kusw.kuauthor | Yan, Jingqi | |
kusw.kuauthor | Zhou, Bo | |
kusw.kuauthor | Shi, Honglian | |
kusw.kudepartment | Pharmacology and Toxicology | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.1371/journal.pone.0027798 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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Pharmacy Scholarly Works [299]