title: Sulfonylurea Receptor 1 in Humans with Post-Traumatic Brain Contusions.
abstract: Post-traumatic brain contusions (PTBCs) are traditionally considered primary injuries and can increase in size, generate perilesional edema, cause mass effect, induce neurological deterioration, and cause death. Most patients experience a progressive increase in pericontusional edema, and nearly half, an increase in the hemorrhagic component itself. The underlying molecular pathophysiology of contusion-induced brain edema and hemorrhagic progression remains poorly understood. The aim of this study was to investigate sulfonylurea 1/transient receptor potential melastatin 4 (SUR1-TRPM4) ion channel SUR1 expression in various cell types (neurons, astrocytes, endothelial cells, microglia, macrophages, and neutrophils) of human brain contusions and whether SUR1 up-regulation was related to time postinjury. Double immunolabeling of SUR1 and cell-type- specific proteins was performed in 26 specimens from traumatic brain injury patients whose lesions were surgically evacuated. Three samples from limited brain resections performed for accessing extra-axial skull-base tumors or intraventricular lesions were controls. We found SUR1 was significantly overexpresed in all cell types and was especially prominent in neurons and endothelial cells (ECs). The temporal pattern depended on cell type: 1) In neurons, SUR1 increased within 48 h of injury and stabilized thereafter; 2) in ECs, there was no trend; 3) in glial cells and microglia/macrophages, a moderate increase was observed over time; and 4) in neutrophils, it decreased with time. Our results suggest that up-regulation of SUR1 in humans point to this channel as one of the important molecular players in the pathophysiology of PTBCs. Our findings reveal opportunities to act therapeutically on the mechanisms of growth of traumatic contusions and therefore reduce the number of patients with neurological deterioration and poor neurological outcomes.
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Tamara
authors.initials: T
authors.lastname: Martínez-Valverde
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Marian
authors.initials: M
authors.lastname: Vidal-Jorge
authors.affiliation: 2 Department of Pathology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez-Saez
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Lidia
authors.initials: L
authors.lastname: Castro
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .|3 Department of Neurosurgery, Vall d'Hebron University Hospital , Universitat Autònoma de Barcelona, Barcelona, Spain .
authors.forename: Fuat
authors.initials: F
authors.lastname: Arikan
authors.affiliation: 3 Department of Neurosurgery, Vall d'Hebron University Hospital , Universitat Autònoma de Barcelona, Barcelona, Spain .
authors.forename: Esteban
authors.initials: E
authors.lastname: Cordero
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .
authors.forename: Andreea
authors.initials: A
authors.lastname: Rădoi
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .|3 Department of Neurosurgery, Vall d'Hebron University Hospital , Universitat Autònoma de Barcelona, Barcelona, Spain .
authors.forename: Maria-Antonia
authors.initials: MA
authors.lastname: Poca
authors.affiliation: 4 Departments of Neurosurgery, Physiology and Pathology, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
authors.affiliation: 1 Neurotraumatology and Neurosurgery Research Unit (UNINN), Universitat Autònoma de Barcelona , Barcelona, Spain .|3 Department of Neurosurgery, Vall d'Hebron University Hospital , Universitat Autònoma de Barcelona, Barcelona, Spain .
authors.forename: Juan
authors.initials: J
authors.lastname: Sahuquillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001929:Brain Edema / Q000209:etiology; D020201:Brain Hemorrhage, Traumatic / Q000235:genetics / Q000378:metabolism; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D003288:Contusions / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011446:Prospective Studies; D064233:Sulfonylurea Receptors / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C577507:ABCC8 protein, human; D064233:Sulfonylurea Receptors; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human
keywords: brain contusion; brain edema; human; immunofluorescence; sulfonyurea receptor 1