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Title: Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence. Author: Jha RM, Bell J, Citerio G, Hemphill JC, Kimberly WT, Narayan RK, Sahuquillo J, Sheth KN, Simard JM. Journal: Int J Mol Sci; 2020 Jan 09; 21(2):. PubMed ID: 31936452. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]