Hypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide.
AuthorIrvine, Hannah J
Hinson, H E
Molyneaux, Bradley J
Simard, J Marc
Sheth, Kevin N
Kimberly, W Taylor
JournalCell Reports. Medicine
MetadataShow full item record
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.
Rights/TermsCopyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/19186
- Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction.
- Authors: Vorasayan P, Bevers MB, Beslow LA, Sze G, Molyneaux BJ, Hinson HE, Simard JM, von Kummer R, Sheth KN, Kimberly WT
- Issue date: 2019 Nov
- Long-Term Outcomes in Patients Aged ≤70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction: An Exploratory Analysis.
- Authors: Sheth KN, Petersen NH, Cheung K, Elm JJ, Hinson HE, Molyneaux BJ, Beslow LA, Sze GK, Simard JM, Kimberly WT
- Issue date: 2018 Jun
- BIIB093 (intravenous glibenclamide) for the prevention of severe cerebral edema.
- Authors: Griepp DW, Lee J, Moawad CM, Davati C, Runnels J, Fiani B
- Issue date: 2021
- Glyburide is associated with attenuated vasogenic edema in stroke patients.
- Authors: Kimberly WT, Battey TW, Pham L, Wu O, Yoo AJ, Furie KL, Singhal AB, Elm JJ, Stern BJ, Sheth KN
- Issue date: 2014 Apr
- Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial.
- Authors: Kimberly WT, Bevers MB, von Kummer R, Demchuk AM, Romero JM, Elm JJ, Hinson HE, Molyneaux BJ, Simard JM, Sheth KN
- Issue date: 2018 Dec 4