Receptor for advanced glycation end products and neuronal deficit in the fatal brain edema of diabetic ketoacidosis

William H. Hoffman, Carol M. Artlett, Weixian Zhang, Christian W. Kreipke, Gregory G Passmore, Jose A. Rafols, Anders A.F. Sima

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)154-162
Number of pages9
JournalBrain Research
Volume1238
DOIs
Publication statusPublished - Oct 31 2008

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Keywords

  • Astrocytosis
  • Diabetic encephalopathy
  • Diabetic ketoacidosis
  • Neuroinflammation
  • Neuronal deficit
  • White matter atrophy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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