The
sulfonylurea receptor 1 (Sur1)-transient receptor potential 4 (Trpm4) channel is an important molecular
element in focal
cerebral ischemia. The channel is upregulated in all cells of the neurovascular unit following
ischemia, and is linked to microvascular dysfunction that manifests as
edema formation and secondary
hemorrhage, which cause
brain swelling. Activation of the channel is a major molecular mechanism of cytotoxic
edema and "accidental necrotic cell death." Blockade of Sur1 using
glibenclamide has been studied in different types of rat models of
stroke: (i) in conventional non-lethal models (thromboembolic, 1-2 h temporary, or permanent
middle cerebral artery occlusion),
glibenclamide reduces
brain swelling and
infarct volume and improves neurological function; (ii) in lethal models of malignant
cerebral edema,
glibenclamide reduces
edema, brain swelling, and mortality; (iii) in models with rtPA,
glibenclamide reduces swelling, hemorrhagic transformation, and death. Retrospective studies of diabetic patients who present with
stroke have shown that those whose diabetes is managed with a sulfonylurea
drug and who are maintained on the sulfonylurea
drug during hospitalization for
stroke have better outcomes at discharge and are less likely to suffer hemorrhagic transformation. Here, we provide a comprehensive review of the basic science, preclinical experiments, and retrospective clinical studies on
glibenclamide in focal
cerebral ischemia and
stroke. We also compare the preclinical work in
stroke models to the updated recommendations of the
Stroke Therapy Academic Industry Roundtable (STAIR). The findings reviewed here provide a strong foundation for a translational research program to study
glibenclamide in patients with
ischemic stroke.