Citation

Jha RM, Bell J, Citerio G, Hemphill JC, Kimberly WT, Narayan RK, Sahuquillo J, Sheth KN, Simard JM. Int. J. Mol. Sci. 2020; 21(2): e409.

Affiliation

Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Copyright

(Copyright © 2020, Molecular Diversity Preservation International)

DOI

10.3390/ijms21020409

PMID

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.

Language: en

Keywords

ASTRAL; SUR1 (Sulfonylurea receptor 1); TBI (traumatic brain injury); TRPM4 (transient receptor potential melastatin 4); cerebral edema; contusion expansion; glibenclamide; glyburide