Glyburide is associated with attenuated vasogenic edema in stroke patients.
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.
Center for Human Genetic Research and Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, wtkimberly@partners.org.
W Taylor
WT
Kimberly
Thomas W K
TW
Battey
Ly
L
Pham
Ona
O
Wu
Albert J
AJ
Yoo
Karen L
KL
Furie
Aneesh B
AB
Singhal
Jordan J
JJ
Elm
Barney J
BJ
Stern
Kevin N
KN
Sheth
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001929:Brain Edema / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000097:blood / Q000150:complications / Q000175:diagnosis; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D011897:Random Allocation; D012189:Retrospective Studies; D020521:Stroke / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D016896:Treatment Outcome
D015415:Biomarkers; D007004:Hypoglycemic Agents; D020780:Matrix Metalloproteinase 9; D005905:Glyburide