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

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    Author
    Jha, R.M.
    Bell, J.
    Simard, J.M.
    Date
    2020
    Journal
    International journal of molecular sciences
    Publisher
    MDPI
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/ijms21020409
    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.
    Keyword
    ASTRAL
    cerebral edema
    contusion expansion
    glibenclamide
    glyburide
    SUR1 (Sulfonylurea receptor 1)
    TBI (traumatic brain injury)
    TRPM4 (transient receptor potential melastatin 4)
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077855834&doi=10.3390%2fijms21020409&partnerID=40&md5=3cadbb03b34dda71dd594f2ad5cc5ed0; http://hdl.handle.net/10713/11677
    ae974a485f413a2113503eed53cd6c53
    10.3390/ijms21020409
    Scopus Count
    Collections
    UMB Open Access Articles 2020

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