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Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients

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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 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.

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Acknowledgments

This work was supported by the National Institutes of Health/National Institute of Neurological Diseases and Stroke (K23 NS076597, W.T.K.). Some of the samples and data used in this research were originally collected with funding through the NIH (P50 NS051343, K.L.F. and R01 NS051412, A.B.S.) or through Remedy Pharmaceuticals, Inc (GAMES-Pilot study).

Disclosures

W.T.K discloses a research Grant (NIH; significant). The GAMES-Pilot study (NCT01268683) was funded by Remedy Pharmaceuticals, Inc. and the sponsor had no role in the preparation of this manuscript.

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Authors and Affiliations

  1. Center for Human Genetic Research and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    W. Taylor Kimberly, Thomas W. K. Battey & Ly Pham

  2. Athinoulo A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    W. Taylor Kimberly & Ona Wu

  3. Stroke Service, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    W. Taylor Kimberly & Aneesh B. Singhal

  4. Division of Neuroradiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Albert J. Yoo

  5. Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Karen L. Furie

  6. Division of Biostatistics and Epidemiology, Medical University of South Carolina, Charleston, NC, USA

    Jordan J. Elm

  7. Department of Neurology and Emergency Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Barney J. Stern

  8. Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale Medical School and Yale New Haven Hospital, New Haven, CT, USA

    Kevin N. Sheth

  9. Lunder 644, 55 Fruit St, Boston, MA, 02114, USA

    W. Taylor Kimberly

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  1. W. Taylor Kimberly
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Correspondence to W. Taylor Kimberly.

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Kimberly, W.T., Battey, T.W.K., Pham, L. et al. Glyburide is Associated with Attenuated Vasogenic Edema in Stroke Patients. Neurocrit Care 20, 193–201 (2014). https://doi.org/10.1007/s12028-013-9917-z

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  • DOI: https://doi.org/10.1007/s12028-013-9917-z

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