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dc.contributor.authorIrvine, Hannah J
dc.contributor.authorAcharjee, Animesh
dc.contributor.authorWolcott, Zoe
dc.contributor.authorAment, Zsuzsanna
dc.contributor.authorHinson, H E
dc.contributor.authorMolyneaux, Bradley J
dc.contributor.authorSimard, J Marc
dc.contributor.authorSheth, Kevin N
dc.contributor.authorKimberly, W Taylor
dc.date.accessioned2022-06-16T13:37:09Z
dc.date.available2022-06-16T13:37:09Z
dc.date.issued2022-06-09
dc.identifier.urihttp://hdl.handle.net/10713/19186
dc.description.abstractBrain edema after a large stroke causes significant morbidity and mortality. Here, we seek to identify pharmacodynamic markers of edema that are modified by intravenous (i.v.) glibenclamide (glyburide; BIIB093) treatment. Using metabolomic profiling of 399 plasma samples from patients enrolled in the phase 2 Glyburide Advantage in Malignant Edema and Stroke (GAMES)-RP trial, 152 analytes are measured using liquid chromatography-tandem mass spectrometry. Associations with midline shift (MLS) and the matrix metalloproteinase-9 (MMP-9) level that are further modified by glibenclamide treatment are compared with placebo. Hypoxanthine is the only measured metabolite that associates with MLS and MMP-9. In sensitivity analyses, greater hypoxanthine levels also associate with increased net water uptake (NWU), as measured on serial head computed tomography (CT) scans. Finally, we find that treatment with i.v. glibenclamide reduces plasma hypoxanthine levels across all post-treatment time points. Hypoxanthine, which has been previously linked to inflammation, is a biomarker of brain edema and a treatment response marker of i.v. glibenclamide treatment.en_US
dc.description.urihttps://doi.org/10.1016/j.xcrm.2022.100654en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofCell Reports. Medicineen_US
dc.rightsCopyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.en_US
dc.subjectbrain edemaen_US
dc.subjectglibenclamideen_US
dc.subjecthypoxanthineen_US
dc.subjectinflammationen_US
dc.subjectmetabolismen_US
dc.subjectmetabolomicsen_US
dc.subjectstrokeen_US
dc.titleHypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide.en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.xcrm.2022.100654
dc.identifier.pmid35700741
dc.source.journaltitleCell reports. Medicine
dc.source.beginpage100654
dc.source.endpage
dc.source.countryUnited States


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