Hyperglycemia and Traumatic Brain Injury

The experiments described in this grant will investigate the relationship between hyperglycemia and outcome following traumatic brain injury (TBI). We hypothesize that having hyperglycemia as a pre-existing condition at the time of trauma will significantly impact outcome. Many adults who are overweight or obese, develop hyperglycemia and insulin resistant type 2 diabetes. As a model we have chosen to use the Zucker fatty (ZDF) rat because it becomes obese and develops insulin resistant hyperglycemia. In the proposed experiments, ZDF rats will be subjected to a laterally placed cortical contusion. They will be compared to Zucker lean (ZL) rats that do not develop hyperglycemia. The injured animals will be examined for changes in behavior using a novel working memory task (delayed-non-matching-to-place) and a spatial memory task. Other experiments will probe changes in hippocampal electrophysiology and changes in morphology. Since oxidative stress is a common feature in TBI, studies will explore how a hyperglycemic condition might exacerbate this important pathophysiology. In these studies we will examine how the hyperglycemic condition alters antioxidant systems and monitor changes in important synaptic components in both the cortex and hippocampus. If a pre-existing condition of hyperglycemia exacerbates the brain's response to injury, then individuals with this metabolic condition need to be identified early upon admission and treated differently than individuals without hyperglycemia.