Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury : A Review of the Evidence
Jha, Ruchira M. (University of Pittsburgh)
Bell, Josh (Biogen (Estats Units d'Amèrica))
Citerio, Giuseppe (Ospedale San Gerardo (Itàlia))
Hemphill, J. Claude (University of California)
Kimberly, W. Taylor (Massachusetts General Hospital (Boston))
Narayan, Raj K. (North Shore University Hospital)
Sahuquillo Barris, Juan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sheth, Kevin N. (Yale University School of Medicine)
Simard, J. Marc (University of Maryland School of Medicine)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	SUR1 (Sulfonylurea receptor 1) ; TRPM4 (transient receptor potential melastatin 4) ; TBI (traumatic brain injury) ; Cerebral edema ; Contusion expansion ; Glibenclamide ; Glyburide ; ASTRAL
Publicat a:	International journal of molecular sciences, Vol. 21 (january 2020) , ISSN 1422-0067

DOI: 10.3390/ijms21020409
PMID: 31936452

30 p, 5.9 MB

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