Hypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide

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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.accessioned2024-06-25T14:02:56Z
dc.date.available2024-06-25T14:02:56Z
dc.date.issued2022-06-13
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.identifier.citationIrvine HJ, Acharjee A, Wolcott Z, Ament Z, Hinson HE, Molyneaux BJ, Simard JM, Sheth KN, Kimberly WT. Hypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide. Cell Rep Med. 2022 Jun 21;3(6):100654. doi: 10.1016/j.xcrm.2022.100654. Epub 2022 Jun 13en_US
dc.identifier.doi10.1016/j.xcrm.2022.100654
dc.identifier.eissn2666-3791
dc.identifier.pmid35700741
dc.identifier.urihttp://hdl.handle.net/20.500.14200/4956
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.relation.urlhttps://www.sciencedirect.com/journal/cell-reports-medicineen_US
dc.source.journaltitleCell Reports Medicineen_US
dc.subjectGeneticsen_US
dc.subjectSurgeryen_US
dc.subjectMicrobiology. Immunologyen_US
dc.subjectOncology. Pathology.en_US
dc.titleHypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamideen_US
dc.typeArticleen_US
dspace.entity.typePublication
oa.grant.openaccessnaen_US
rioxxterms.versionNAen_US
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