Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence

Authors

Ruchira M. Jha, Departments of Critical Care Medicine, Neurology, Neurological Surgery, Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA 15201, USA.Follow
Josh Bell, Biogen, Cambridge, MA 02142, USA.
Giuseppe Citerio, School of Medicine and Surgery, University of Milan-Bicocca, 20121 Milan, Italy.
J Claude Hemphill, Department of Neurology, University of California, San Francisco, CA 94110, USA.
W Taylor Kimberly, Division of Neurocritical Care and Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Boston, MA 02108, USA.
Raj K. Narayan, Department of Neurosurgery, North Shore University Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY 11030, USA.
Juan Sahuquillo, Neurotrauma and Neurosurgery Research Unit (UNINN), Vall d'Hebron Research Institute (VHIR), 08001 Barcelona, Spain.
Kevin N. Sheth, Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale University School of Medicine, New Haven, CT 06501, USA.
J Marc Simard, Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Document Type

Article

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.

Medical Subject Headings

Animals; Brain Injuries, Traumatic (drug therapy, genetics, metabolism); Clinical Trials as Topic; Genetic Variation; Glyburide (therapeutic use); Humans; Sulfonylurea Receptors (metabolism); TRPM Cation Channels (metabolism)

Publication Date

1-9-2020

Publication Title

International journal of molecular sciences

E-ISSN

1422-0067

Volume

21

Issue

2

PubMed ID

31936452

Digital Object Identifier (DOI)

10.3390/ijms21020409

Recommended Citation

Jha, Ruchira M.; Bell, Josh; Citerio, Giuseppe; Hemphill, J Claude; Kimberly, W Taylor; Narayan, Raj K.; Sahuquillo, Juan; Sheth, Kevin N.; and Simard, J Marc, "Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence" (2020). Neurology. 1363.
https://scholar.barrowneuro.org/neurology/1363