Oxidative damage is present in the fatal brain edema of diabetic ketoacidosis.
Oxidative stress is implicated as a pathogenic factor in a spectrum of chronic diseases, notably, neurodegenerative disease. Noteworthy in this regard is that type 1 diabetes mellitus (T1DM) results in oxidative stress, leading to systemic complications of T1DM. We hypothesized that oxidative stress associated with diabetic ketoacidosis (DKA) of T1DM might have measurable brain sequelae. Consistent with this hypothesis are neurohistology and neuroradiologic studies of T1DM that suggest oxidative insults are involved in the chronic complications of diabetic encephalopathy. To further address the role of oxidative stress in an acute setting, specifically in fatal brain edema (BE) associated with DKA, we studied neuronal localization and levels of oxidative stress markers reported to be increased in other neurodegenerative conditions. We demonstrated increased levels of 8-hydroxyguanosine (8OHG), 4-hydroxynonenal (HNE), and heme oxygenase-1 (HO-1) in the pyramidal neurons of the hippocampus of DKA BE in comparison to controls. However, in the cerebellum, only 8OHG was increased in the Purkinje cells and other cells of the molecular layer. These results indicate a role for oxidative stress in the pathogenesis of T1DM encephalopathy.
Department of Pediatrics, Section of Pediatric Endocrinology, Medical College of Georgia, 1120 15th Street BG-1007Augusta, GA 30912, USA. whoffman@mail.mcg.edu
William H
WH
Hoffman
Sandra L
SL
Siedlak
Yang
Y
Wang
Rudy J
RJ
Castellani
Mark A
MA
Smith
D000293:Adolescent; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016883:Diabetic Ketoacidosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000096:biosynthesis; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology
D006151:Guanosine; C046215:8-hydroxyguanosine; D051547:Heme Oxygenase-1