title: Inflammatory mediators and blood brain barrier disruption in fatal brain edema of diabetic ketoacidosis.
abstract: Brain edema (BE) is an uncommon but life-threatening complication of severe diabetic ketoacidosis (DKA) and its treatment. Despite advances in treatment of DKA, the pathogenesis of both initiation and progression of the associated BE is unclear. In the present study we examined the blood brain barrier (BBB) integrity and the potential involvement of the inflammatory mediators in BBB breakdown in two cases of fatal BE associated with DKA. In both cases there were typical signs of disruption of the BBB manifested by the absence of tight junction proteins (occludin, claudin-5, ZO-1 and JAM-1) in the parenchymal blood vessels, as well as albumin extravasation in examined brain areas. The neuroinflammatory markers chemokine CCL2, NF-kappaB and nitrotyrosine were localized in the perivascular areas of the disrupted BBB and diffusely distributed in the brain parenchyma. Our data indicate that neuroinflammation plays a role in the BBB disruption of the fatal BE of DKA.
authors.affiliation: Department of Pediatrics, Section of Pediatric Endocrinology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Hoffman
authors.forename: Svetlana M
authors.initials: SM
authors.lastname: Stamatovic
authors.forename: Anuska V
authors.initials: AV
authors.lastname: Andjelkovic
mesh_terms: D000293:Adolescent; D000418:Albumins / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D062507:Claudin-5; D016883:Diabetic Ketoacidosis / Q000150:complications* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D000418:Albumins; C107466:CLDN5 protein, human; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D062507:Claudin-5; C407243:F11R protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C002744:3-nitrotyrosine; D014443:Tyrosine