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.