title: Diabetic ketoacidosis in juvenile rats is associated with reactive gliosis and activation of microglia in the hippocampus.
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.
authors.affiliation: Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: Weei
authors.initials: W
authors.lastname: Lo
authors.affiliation: Departments of Physiology and Membrane Biology, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: O'Donnell
authors.affiliation: Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tancredi
authors.affiliation: Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: Myra
authors.initials: M
authors.lastname: Orgain
authors.affiliation: Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Glaser
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D034961:Antigens, Nuclear / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016883:Diabetic Ketoacidosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D034961:Antigens, Nuclear; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C546339:Rbfox3 protein, rat
keywords: brain injury; cerebral edema; diabetic ketoacidosis; hippocampus