Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 09, 2020
- Source ID
- 10.3390/ijms21020409
Entities
People
- Giuseppe Citerio
- J Marc Simard
- J. Claude Hemphill
- Josh Bell
- Juan Sahuquillo
- Kevin N. Sheth
- Raj K. Narayan
- Ruchira Menka Jha
- W. Taylor Kimberly
Organizations
- American Heart Association
- Mental Illness Research, Education and Clinical Centers
- National Heart, Lung, and Blood Institute
- National Institute of Neurological Disorders and Stroke
- United States Department of Defense