Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to 
decrease edema after subarachnoid hemorrhage. We investigated if inhibiting SUR1 
reduces cerebral edema due to metastases, the most common brain tumor, and 
explored the putative association of SUR1 and the endothelial tight junction 
protein, zona occludens-1 (ZO-1). Nude rats were intracerebrally implanted with 
small cell lung carcinoma (SCLC) LX1 or A2058 melanoma cells (n = 36). Rats were 
administered vehicle, glyburide (4.8 µg twice, orally), or dexamethasone (0.35 
mg, intravenous). Blood-tumor barrier (BTB) permeability (K (trans)) was 
evaluated before and after treatment using dynamic contrast-enhanced magnetic 
resonance imaging. SUR1 and ZO-1 expression was evaluated using 
immunofluorescence and Western blots. In both models, SUR1 expression was 
significantly increased (P < .05) in tumors. In animals with SCLC, control mean 
K (trans) (percent change ± standard error) was 101.8 ± 36.6%, and both 
glyburide (-21.4 ± 14.2%, P < .01) and dexamethasone (-14.2 ± 13.1%, P < .01) 
decreased BTB permeability. In animals with melanoma, compared to controls 
(117.1 ± 43.4%), glyburide lowered BTB permeability increase (3.2 ± 15.4%, P < 
.05), while dexamethasone modestly lowered BTB permeability increase (63.1 ± 
22.1%, P > .05). Both glyburide (P < .001) and dexamethasone (P < .01) decreased 
ZO-1 gap formation. By decreasing ZO-1 gaps, glyburide was at least as effective 
as dexamethasone at halting increased BTB permeability caused by SCLC and 
melanoma. Glyburide is a safe, inexpensive, and efficacious alternative to 
dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.