TBI & Alcohol Abuse: Co-occurring Conditions that Enhance Brain Damage

描述(由申请人提供)： 项目摘要/摘要创伤性脑损伤(TBI)由头部的打击引起，其严重程度从轻微(例如，精神状态或意识的短暂变化)到严重(例如，长期昏迷、长期健忘、认知功能改变)不等。大脑损伤是最有可能导致死亡或永久残疾的损伤类型。全面预算外投资的成本 以任何标准衡量，我们的社会都是庞大的。在普通人群中，脑外伤的风险在整个生命周期内相当稳定，但军事人员的风险要高得多。事实上，在阿富汗和伊拉克服役的士兵和海军陆战队士兵所遭受的“标志性”伤害就是创伤性脑损伤，约占所有战斗伤亡的30%。据估计，目前冲突中有10%至20%的退伍军人(15万至30万人)患有某种脑损伤。鉴于多个器官系统可以改变的事实，脑外伤被最准确地归类为多发伤。更重要的是，即使是轻微的脑外伤，其影响也是累积的，可能会增加涉及中枢神经系统的共病疾病的风险，如创伤后应激障碍和帕金森氏症。尤其是药物滥用和酒精滥用，是创伤性脑损伤的一个主要复杂因素，本身也应被视为一种并存的情况。酒精滥用在现役军人中稳步增加，长期以来一直是退伍军人中的严重问题。与脑外伤一样，酒精滥用也会对中枢神经系统造成损害，但人们对酒精如何影响脑外伤的严重程度和结局知之甚少。认识到酗酒和脑外伤对风险和后果是双向相关的，这一应用领域的研究目标是更好地了解这两种情况是如何相互作用来决定长期结果的。为了实现这一目标，特定目标1将分析在脑损伤前过量饮酒如何改变脑损伤的主要体征和症状，包括水肿、低灌流、炎症增加、神经元损伤和认知能力下降。特定目标2将评估在脑外伤后酗酒治疗时这些相同的结果指标。具体目标3将确定脑损伤是否随后增加自愿酒精摄入量。我们将使用经过验证的闭合性头部损伤和酗酒的小鼠模型来实现这一应用程序的目标。

DESCRIPTION (provided by applicant): Project summary/abstract Traumatic brain injury (TBI) results from a blow to the head and can range in severity from mild (e.g., brief change in mental status or consciousness) to severe (e.g., extended unconsciousness, prolonged amnesia, altered cognitive function). Trauma to the brain is the most likely type of injury to cause death or permanent disability. The costs of TBI to our society are enormous when measured by any criterion. In the general population, the risk of TBI is fairly constant throughout the lifespan, but military personnel are at much higher risk. In fact, TBI has been coined the "signature" injury suffered by soldiers and marines serving in Afghanistan and Iraq and accounts for about 30% of all combat casualties. It has been estimated that 10-20% of veterans of the current conflicts (150,000-300,000) have TBI of some kind. TBI is most accurately classified as a polytrauma in light of the fact that multiple organ systems can be altered. What is more, the effects of even mild TBI are cumulative and can increase the risk of co-morbid illnesses involving the central nervous system such as PTSD and Parkinson's disease. Substance abuse and alcohol abuse in particular, is a major complicating factor in TBI and should also be considered as a co-occurring condition in its own right. Alcohol abuse is steadily increasing among active military personnel and has long been a serious affliction among veterans. Like TBI, alcohol abuse can cause damage to the CNS but very little is known about how alcohol influences the severity and outcome of TBI. Recognizing that alcohol abuse and TBI are bi-directionally related for risk and consequences, the goal of research in this application is to achieve a better understanding of how these two conditions interact to determine long-term outcomes. To achieve this goal, Specific Aim 1 will analyze how binge alcohol intake prior to TBI alters the major signs and symptoms of brain injury to include edema, hypoperfusion, increased inflammation, neuronal damage, and diminished cognitive ability. Specific Aim 2 will evaluate these same outcome measures when binge alcohol treatment follows TBI. Specific Aim 3 will determine if TBI subsequently increases voluntary intake of alcohol. We will use validated mouse models of closed head injury and binge alcohol intoxication to pursue the goals of this application.