Effects of hyperglycemia on the developing brain in newborns

Pediatr Neurol. 2014 Aug;51(2):239-45. doi: 10.1016/j.pediatrneurol.2014.04.015. Epub 2014 Apr 18.


Background: Hyperglycemia is a common problem in preterm neonates and is associated with increased risk of mortality and severe morbidities such as brain damage. However, available data about the effects of severity of hyperglycemia on the developing brain in the early life is limited. Therefore, we evaluated the effects of moderate and severe hyperglycemia on the developing brain.

Method: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as control, moderate hyperglycemia (30% dextrose), and severe hyperglycemia (50% dextrose). Pups in the hyperglycemia groups were administered subcutaneous sterile dextrose solution at a dose of 4 mL/kg daily from the second day to the eleventh day of life. Blood glucose levels were measured every day in all study groups. Rat brain tissues were removed at the end of the study. Histopathologic and immunohistochemical (caspase-9, -8, and -3) examination and biochemical analysis including xanthine oxidase, total antioxidant status, total oxidant status, and malondialdehyde activities were performed.

Results: Weight of the brain tissues in rats with hyperglycemia groups was significantly lower than the control group (P < 0.05). Weight of the brain tissues in rats with moderate hyperglycemia was lower than that of the severe hyperglycemia (P < 0.05). In the histopathologic and immunochemical evaluation, severity of brain damage and apoptosis were significantly higher in the severe hyperglycemia group, especially at the level of the hippocampus (P < 0.05). Tissue malondialdehyde, xanthine oxidase levels, and total oxidant status were significantly increased in the severe hyperglycemia group, whereas total antioxidant status was significantly decreased in the severe hyperglycemia group (P < 0.001).

Conclusion: Brain damaging effects of severe hyperglycemia were observed in the developing brains of the rat pups. It might be inferred that severe hyperglycemia can damage the developing brain especially in preterm infants.

Keywords: developing brain; hyperglycemia; newborn; preterm; rat.

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis*
  • Blood Glucose
  • Brain / metabolism*
  • Brain / pathology*
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hyperglycemia / blood
  • Hyperglycemia / complications*
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index


  • Blood Glucose