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。 公共卫生相关性： 项目叙述创伤性脑损伤(TBI)是一个严重的公共和军事卫生问题。颅脑损伤给我们的社会带来的严重代价有多种形式，包括长期残疾、长期康复所需的具有挑战性的课程以及与治疗和康复相关的费用。酗酒也是一个严重的公共卫生保健问题。脑外伤和酗酒是并存的情况，两者都会增加彼此相关的风险和问题。与平民相比，现役军人和退伍军人在这两种情况下面临的风险更高，似乎只有合乎逻辑的说法才会表明酗酒会加重脑损伤，反之亦然。然而，迄今为止关于酒精与脑外伤相互作用的临床和基础研究的结果令人惊讶地自相矛盾，一些报告说酒精会恶化脑损伤，另一些报告说酒精会减轻脑损伤的影响，还有一些报告说酒精不会改变脑损伤。鉴于酒精滥用在脑外伤中的普遍存在，并考虑到人们对这些条件如何相互作用来决定长期结果知之甚少，我们必须更好地了解它们相互作用的性质。

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. PUBLIC HEALTH RELEVANCE: Project Narrative Traumatic brain injury (TBI) is a serious public and military health problem. The severe cost of TBI to our society is seen in many forms and includes long-term disability, the challenging courses taken by prolonged rehabilitation, and the expense associated with treatment and recovery. Alcohol abuse is also a serious public health care concern. TBI and alcohol abuse are co-occurring conditions and each can increase the risks and problems associated with the other. Active military personnel and veterans are at higher risk for both conditions by comparison to civilians and it only seems logical to suggest that alcohol abuse would worsen TBI and vice versa. However, the results from clinical and basic studies to date on alcohol-TBI interactions are surprisingly paradoxical in that some report that alcohol worsens TBI, others report that alcohol lessens the effects of TBI, and still others report that alcohol dos not alter TBI. In view of the prevalence of alcohol abuse in TBI, and considering how little is known about how these conditions interact to determine long-term outcomes, it is imperative that we achieve a better understanding of the nature of their interactions.