TY  - JOUR
PY  - 2020//
TI  - Role of sulfonylurea receptor 1 and glibenclamide in traumatic brain injury: a review of the evidence
JO  - International journal of molecular sciences
A1  - Jha, Ruchira M.
A1  - Bell, Josh
A1  - Citerio, Giuseppe
A1  - Hemphill, J. Claude
A1  - Kimberly, W. Taylor
A1  - Narayan, Raj K.
A1  - Sahuquillo, Juan
A1  - Sheth, Kevin N.
A1  - Simard, J. Marc
SP  - e409
EP  - e409
VL  - 21
IS  - 2
N2  - 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. <br><br>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.<p />  <p>Language: en</p>
LA  - en
SN  - 1661-6596
UR  - http://dx.doi.org/10.3390/ijms21020409
ID  - ref1
ER  -