Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence
JournalInternational journal of molecular sciences
MetadataShow full item record
AbstractCerebral 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.
SUR1 (Sulfonylurea receptor 1)
TBI (traumatic brain injury)
TRPM4 (transient receptor potential melastatin 4)
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85077855834&doi=10.3390%2fijms21020409&partnerID=40&md5=3cadbb03b34dda71dd594f2ad5cc5ed0; http://hdl.handle.net/10713/11677
- BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema.
- Authors: Pergakis M, Badjatia N, Chaturvedi S, Cronin CA, Kimberly WT, Sheth KN, Simard JM
- Issue date: 2019 Dec
- Sulfonylurea Receptor 1, Transient Receptor Potential Cation Channel Subfamily M Member 4, and KIR6.2:Role in Hemorrhagic Progression of Contusion.
- Authors: Gerzanich V, Stokum JA, Ivanova S, Woo SK, Tsymbalyuk O, Sharma A, Akkentli F, Imran Z, Aarabi B, Sahuquillo J, Simard JM
- Issue date: 2019 Apr 1
- Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date.
- Authors: King ZA, Sheth KN, Kimberly WT, Simard JM
- Issue date: 2018
- Inhibition of the Sur1-Trpm4 channel reduces neuroinflammation and cognitive impairment in subarachnoid hemorrhage.
- Authors: Tosun C, Kurland DB, Mehta R, Castellani RJ, deJong JL, Kwon MS, Woo SK, Gerzanich V, Simard JM
- Issue date: 2013 Dec
- Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.
- Authors: Jha RM, Molyneaux BJ, Jackson TC, Wallisch JS, Park SY, Poloyac S, Vagni VA, Janesko-Feldman KL, Hoshitsuki K, Minnigh MB, Kochanek PM
- Issue date: 2018 Sep 1