Ischemic and
hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant
tissue plasminogen activator,
therapies targeting the underlying pathophysiology of central nervous system (CNS)
ischemia and
hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and
cerebral edema following ischemic insults, and in
neuroinflammation after hemorrhagic
injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial
sulfonylurea receptor 1-transient receptor potential melastatin 4 (Sur1-Trpm4) channels and, in some cases, microglial KATP (Sur1-Kir6.2) channels, with
glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that
glibenclamide and other sulfonylurea agents reduce
infarct volumes,
edema and hemorrhagic conversion, and improve outcomes in rodent models of
ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at
stroke presentation fare better if they continue on
drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of
subarachnoid hemorrhage,
glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of
glibenclamide therapy for CNS
ischemia and
hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest
glibenclamide may be an effective therapeutic option for ischemic and
hemorrhagic stroke.