Receptor for advanced glycation end products and neuronal deficit in the fatal brain edema of diabetic ketoacidosis.
Radiologic and neuropsychologic studies suggest that diabetes mellitus causes structural changes in the brain and adversely effects cognitive development. Experimental animal models of type 1 diabetes mellitus (T1DM) have advanced these findings by demonstrating duration-related neuronal and cognitive deficits in T1DM BB/Wor rats. We studied the expression of receptor for advanced glycation end products (RAGE) and neuronal densities in the brains of two patients who died as the result of clinical brain edema(BE)that developed during the treatment of severe diabetic ketoacidosis (DKA). RAGE was markedly and diffusely expressed in blood vessels, neurons, and the choroid plexus and co-localized with glial fibrillary acidic protein (GFAP) in astrocytes. Significant neuronal loss was seen in the hippocampus and frontal cortex. Astrocytosis was present and white matter was atrophied in both cases when compared to age-matched controls. Our data supports that a neuroinflammatory response occurs in the BE associated with DKA, and that even after a relatively short duration of poorly controlled T1DM, the pathogenesis of primary diabetic encephalopathy can be initiated.
Hoffman
William H
WH
Department of Pediatrics, Section of Pediatric Endocrinology, Medical College of Georgia, Augusta, GA 30912, USA. whoffman@mail.mcg.edu
Artlett
Carol M
CM
Zhang
Weixian
W
Kreipke
Christian W
CW
Passmore
Gregory G
GG
Rafols
Jose A
JA
Sima
Anders A F
AA
D000293:Adolescent; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1; D016883:Diabetic Ketoacidosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009474:Neurons / Q000473:pathology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*
D005904:Glial Fibrillary Acidic Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic