The Effects of Binge Ethanol on Neuroinflammation/Functional Recovery after TBI

描述（由申请人提供）：创伤性脑损伤是死亡和残疾的主要原因，许多人在受伤时受到酒精的影响，遵循酗酒的模式。神经炎症是创伤性脑损伤的结果，酒精已被证明通过与小胶质细胞的相互作用对脑炎症反应具有调节作用。此外，暴露于酗酒会降低新皮层锥体神经元的树突复杂性，导致行为任务的表现不佳。因此，我们假设：创伤性脑损伤前的酒精暴露会使功能结果恶化，并由于神经炎症反应的增加而降低神经元的可塑性。目的#1将确定成年雄性大鼠在急性中毒时给予酗酒酒精方案，随后发生创伤性脑损伤的功能恢复和神经元可塑性。我们将使用感觉运动恢复和高尔基-考克斯染色的敏感性测试来确定神经元树突的可塑性。目的#2将确定成年大鼠在急性中毒时给予酗酒乙醇方案，随后发生创伤性脑损伤的神经炎症反应。我们将确定炎性细胞因子水平，并表征相关脑区的小胶质细胞反应。

DESCRIPTION (provided by applicant): Traumatic brain injury is a major cause of death and disability, and many people are under the influence of alcohol at the time of injury, following a pattern of binge alcohol use. Neuroinflammation is a consequence of traumatic brain injury, and alcohol has been shown to have a modulatory effect on the brain inflammatory response through interactions with microglial cells. Additionally, exposure to binge alcohol decreases dendritic complexity of pyramidal neurons in the neocortex, leading to poor performance on behavioral tasks. Therefore, we hypothesize that: Binge ethanol exposure prior to traumatic brain injury will worsen functional outcome and decrease neuronal plasticity due to an increase in the neuroinflammatory response. Aim #1 will determine functional recovery and neuronal plasticity in adult male rats given a binge ethanol regimen followed by traumatic brain injury while acutely intoxicated. We will use sensitive tests of sensorimotor recovery and golgi-cox staining to determine neuronal dendritic plasticity. Aim #2 will determine the neuroinflammatory response in adult rats given a binge ethanol regimen followed by traumatic brain injury while acutely intoxicated. We will determine inflammatory cytokine levels and characterize the microglial cell response in pertinent brain regions.