High blood glucose does not adversely affect outcome in moderately brain-injured rodents

J Neurotrauma. 2010 Aug;27(8):1439-48. doi: 10.1089/neu.2010.1328.


In a number of clinical studies researchers have reported that acute hyperglycemia is associated with increased mortality and worsened neurological outcome in patients with traumatic brain injury (TBI). In contrast, it has been demonstrated that intensive insulin therapy to lower blood glucose can lead to an increased frequency of hypoglycemic episodes and poor outcome. Consistent with this, experimental and clinical studies have shown that TBI causes a "metabolic crisis" in the injured brain, suggesting that a reduction in glucose availability may exacerbate brain damage. We therefore examined the consequences of hyperglycemia on cognitive and pathological measures. Using a rodent model of TBI, we find that when acute hyperglycemia is induced in animals prior to injury, there is little to no change in motor and cognitive performance, contusion volume, or cerebral edema. To examine the consequences of persistent hyperglycemia (as seen in diabetic patients), animals were treated with streptozotocin (STZ) to induce type 1 diabetes. We find that the presence of persistent STZ-induced hyperglycemia results in a reduction of brain edema. Insulin therapy to reduce blood glucose reverses this beneficial effect of hyperglycemia. Taken together, our results indicate that an acute increase in blood glucose levels may not be harmful, and that intervention with insulin therapy to lower blood glucose levels in TBI patients may increase secondary brain damage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Glucose / physiology*
  • Brain Edema / etiology
  • Brain Edema / pathology
  • Brain Injuries / blood
  • Brain Injuries / pathology*
  • Brain Injuries / psychology*
  • Diabetes Mellitus, Experimental / complications
  • Glucose / pharmacology
  • Hyperglycemia / complications
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Motor Skills / physiology
  • Psychomotor Performance / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Vestibulo-Ocular / physiology


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Glucose