Alcohol exposure exacerbates inflammation and anxiety-like behavior induced by repeated mild TBI during adolescence

摘要

ABSTRACT TBI is the leading cause of death and disability in people under 40 in the United States, with mild TBI (mTBI) being three times more common than moderate and severe injury combined. Currently, there are no effective therapeutics that will preserve or restore brain tissue and function after TBI. As a result, individuals may face a lifetime of deficits. Approximately one in five adolescents self-report having had one or more mild TBI (mTBI) with adolescent athletes being at a higher risk than non-athletic peers. Additionally, adolescents participating in team sports are more likely to take part in alcohol consumption. Both TBI and alcohol are known to cause neuroinflammation, which can be especially damaging to the developing, adolescent brain, including a higher incidence of anxiety reported following either of these insults independently. While mild TBI (mTBI) is the most common, research has shown that the effects of repeated mTBI (rmTBI) over time can build to a level of damage comparable to moderate or even severe injury. Additionally, studies have suggested that the inflammatory effects of TBI during development can lead to an exaggerated inflammatory response to alcohol. In this study, we propose to expose adolescent male and female rats to a series of four mTBIs interspersed with episodes of alcohol exposure to test the hypothesis that while rmTBI and alcohol exposure during adolescence both independently cause neuroinflammation, the combination of these insults will exacerbate this effect, and that this will translate to increases in anxiety-like behavior. Finally, we will treat these animals with the anti- inflammatory drug licofelone to investigate whether post-TBI neuroinflammation can be ameliorated, leading to an improvement in these outcomes.