Diabetic ketoacidosis in juvenile rats is associated with reactive gliosis and activation of microglia in the hippocampus

Pediatr Diabetes. 2016 Mar;17(2):127-39. doi: 10.1111/pedi.12251. Epub 2015 Jan 16.

Abstract

Background: Type 1 diabetes may be associated with structural and functional alterations in the brain. The role of diabetic ketoacidosis (DKA) in causing these alterations has not been well explored.

Methods: We used immunohistochemical staining to investigate cellular alterations in brain specimens from juvenile rats with DKA before, during, and after treatment with insulin and saline, and compared these to samples from diabetic rats and normal controls.

Results: Glial fibrillary acidic protein (GFAP) staining intensity was increased in the hippocampus during DKA and increased further during insulin/saline treatment. Twenty-four and 72 h after treatment, hippocampal GFAP intensity declined but remained above control levels. There were no significant changes in GFAP intensity in the cortex or striatum. OX42 staining intensity was increased during untreated DKA and increased further during insulin/saline treatment in the hippocampus and cortex. NeuN staining intensity was decreased after DKA treatment in the striatum but not in other regions.

Conclusions: DKA causes inflammatory changes in the brain including reactive gliosis and activation of microglia. These findings are present during untreated DKA, but intensify during insulin/saline treatment. The hippocampus was disproportionately affected, consistent with previous studies showing deficits in hippocampal functions in rats after DKA recovery and decreased memory capacity in children with a history of DKA.

Keywords: brain injury; cerebral edema; diabetic ketoacidosis; hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antigens, Nuclear / metabolism
  • CD11b Antigen / metabolism
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Ketoacidosis / complications*
  • Diabetic Ketoacidosis / metabolism
  • Diabetic Ketoacidosis / pathology
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / etiology*
  • Gliosis / metabolism
  • Gliosis / pathology
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Microglia / metabolism
  • Microglia / pathology*
  • Nerve Tissue Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antigens, Nuclear
  • CD11b Antigen
  • CD68 antigen, human
  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat