Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients
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ORIGINAL ARTICLE
Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients W. Taylor Kimberly • Thomas W. K. Battey • Ly Pham • Ona Wu • Albert J. Yoo • Karen L. Furie • Aneesh B. Singhal • Jordan J. Elm Barney J. Stern • Kevin N. Sheth
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Ó Springer Science+Business Media New York 2013
Abstract Background Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Methods Using a case–control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the
Electronic supplementary material The online version of this article (doi:10.1007/s12028-013-9917-z) contains supplementary material, which is available to authorized users. W. T. Kimberly T. W. K. Battey L. Pham Center for Human Genetic Research and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA W. T. Kimberly O. Wu Athinoulo A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA W. T. Kimberly A. B. Singhal Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA W. T. Kimberly (&) Lunder 644, 55 Fruit St, Boston, MA 02114, USA e-mail: [email protected]
glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke. Results We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. Conclusions Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.
K. L. Furie Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA J. J. Elm Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, NC, USA B. J. Stern Department of Neurology and Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, USA K. N. Sheth Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale Medical School and Yale New Haven Hospital, New Haven, CT, USA
A. J. Yoo Division of Neuroradiology, Massach
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