Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence
Date
2020Journal
International journal of molecular sciencesPublisher
MDPIType
Article
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Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.Keyword
ASTRALcerebral edema
contusion expansion
glibenclamide
glyburide
SUR1 (Sulfonylurea receptor 1)
TBI (traumatic brain injury)
TRPM4 (transient receptor potential melastatin 4)
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077855834&doi=10.3390%2fijms21020409&partnerID=40&md5=3cadbb03b34dda71dd594f2ad5cc5ed0; http://hdl.handle.net/10713/11677ae974a485f413a2113503eed53cd6c53
10.3390/ijms21020409