Abstracts

Rationale: In the united states, traumatic brain injury (TBI) occurs in about 2 million people annually, not including the high incidence rates amongst our military personnel. Considering the often devastating outcomes, including post-traumatic epilepsy, understanding the primary and secondary mechanisms involved in TBI is essential. TBI can be studied using various types of animal models that include: lateral fluid percussion injury, controlled cortical impact and impact acceleration injury, including the weight drop method. In these models, pro and anti-inflammatory cytokines are altered after TBI and these inflammatory changes may be related to the primary and secondary symptoms that include edema, cell death and cognitive impairments. Considering that diagnostic tools for the severity and persistence of TBI is lacking, it is important to define the temporal expression patterns of inflammatory proteins in specific regions of the brain following TBI. Although there is a growing literature on this topic, there are significant gaps in the literature. In addition, it is possible that different animal models of TBI produce differential inflammatory profiles. Understanding commonalities between these models might provide further insight into the treatment of brain trauma and the prevention of post-traumatic epilepsy. Therefore, the aim of this study was to characterize the acute biochemical changes of multiple inflammatory cytokines in the rat hippocampus following an impact acceleration injury. Methods: Male Sprague-Dawley rats (200-250gms) were subjected to TBI using a weight-drop version of an impact acceleration injury. A separate group of sham rats served as controls. At 6 or 24 hrs after TBI, animals were euthanized, followed by rapid dissection of the hippocampus. Immediately after extraction, the hippocampus was analyzed for IL-1beta, IL-2, IFN-gamma, GMCSF, VEGF and TNF-alpha using the Luminex system. Results: The results show that in the hippocampus, IL-1beta was significantly decreased between 6 and 24 hr following TBI, whereas TNF-alpha was elevated in TBI rats at 6 hrs after TBI. However, at 24 hours after injury, TNF-alpha was significantly decreased in TBI rats compared to controls. VEGF was also decreased in TBI rats when compared to controls at 24 hr. The data also show a significant increase of IL-2, IFN-gamma and GMCSF between 6 and 24 hrs following TBI. The results suggest that 6 hrs after TBI there is an increased synthesis of the pro-inflammatory TNF-alpha , IFN-gamma and GMCSF which is sustained even after 24 hr. Interestingly, TNF-alpha was significantly decreased in TBI rats compared to controls at the 24 hr timepoint. Conclusions: TBI is a leading cause of epilepsy with a known etiology. Inflammatory signals may be involved in mediating the increased seizure susceptibility that is seen following TBI. The current data add to our growing understanding of the patterns of pro- and anti-inflammatory cytokine expression following TBI.