Neuroinflammatory response of the choroid plexus epithelium in fatal diabetic ketoacidosis.
A systemic inflammatory response (SIR) occurs prior to and during the treatment of severe diabetic ketoacidosis (DKA). IL-1beta, TNF-alpha and C5b-9 are components of SIR and have been speculated to be involved in the clinical brain edema (BE) of DKA. We studied IL-1beta, TNF-alpha, C5b-9, inducible nitric oxide (iNOS), ICAM-1, IL-10 and Hsp70 expression in the brains of two patients who died as the result of clinical BE during the treatment of DKA. IL-1beta was strongly expressed in the choroid plexus epithelium (CPE) and ependyma, and to a lesser extent in the hippocampus, caudate, white matter radiation of the pons, molecular layer of the cerebellum and neurons of the cortical gray matter. TNF-alpha was expressed to a lesser extent than IL-1beta, and only in the CP. C5b-9, previously shown to be deposited on neurons and oligodendrocytes, was found on CPE and ependymal cells. iNOS and ICAM-1 had increased expression in the CPE and ependyma. Hsp70 and IL-10 were also expressed in the CPE of the case with the shorter duration of treatment. Our data demonstrate the presence of a multifaceted neuroinflammatory cytotoxic insult of the CPE, which may play a role in the pathophysiology of the fatal brain edema of DKA.
Hoffman
William H
WH
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA.
Casanova
Manuel F
MF
Cudrici
Cornelia D
CD
Zakranskaia
Ekaterina
E
Venugopalan
Roopa
R
Nag
Sukriti
S
Oglesbee
Michael J
MJ
Rus
Horea
H
D000293:Adolescent; D017209:Apoptosis; D018957:CD59 Antigens / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism* / Q000473:pathology*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D016883:Diabetic Ketoacidosis / Q000378:metabolism* / Q000473:pathology*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018957:CD59 Antigens; D015938:Complement Membrane Attack Complex; D018840:HSP70 Heat-Shock Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II