Dietary influences on closed-head traumatic brain injury in a pediatric rodent model

Traumatic brain injury (TBI) is one of the most common causes of emergency room visits in children, and it is a leading cause of death in juveniles in the United States. Similarly, a high proportion of this population consumes diets high in saturated fats, and millions of children are overweight or obese. Therefore, the goal of the present study was to assess the relationship between diet and TBI outcomes in juvenile rats. In the current study, groups of juvenile male Long Evans rats were provided with a combination of a high fat diet (HFD) and a solution of 10% high-fructose corn syrup or a standard chow diet. The animals were trained on the Morris water maze (MWM) for two consecutive days to test spatial learning. Rats were then subjected to either mild TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) or sham procedures. Immediately after TBI, the animals' righting reflexes were tested. Animals were retested in the MWM either three hours or four days post-injury. The animals were euthanized either four days or seven days post-injury, and brain samples and blood plasma were collected for QRT-PCR, immunohistochemistry, and triglyceride assays. Acute HFD intake did not alter the body weight of the weanling rats, but the HFD significantly elevated triglyceride levels by two weeks. Latency to the platform during the MWM training period was not affected by diet. Nor were there any differences in post-injury time to righting and walking by diet group. However, the TBI rats' time to righting and walking was significantly reduced compared to the sham rats, p < 0.05. The latency and distance traveled to the platform in the MWM were significantly increased by TBI three hours post-injury. Alternately, these changes were abolished four days post-injury. QRT-PCR revealed that CREB1 and IL1β were increased in the hippocampus. On the other hand, IL6 was increased in the prefrontal cortex as a function of injury. CREB1, IL1β, and IL6 gene expression were significantly elevated by TBI, while CLDN5, IL6, and IL1R1 were increased in the hippocampus due to diet. Immunohistochemistry revealed an increased immunoreactivity of IBA-1 in the cortex and corpus callosum in the TBI animals, regardless of diet. The results from this study offer evidence that both HFD and TBI influence behavior and biochemical markers in juvenile rats using the novel CHIMERA device. © FASEB.