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

描述（由申请人提供）： 创伤性脑损伤（TBI）是由头部受到打击引起的，严重程度从轻度（例如，精神状态或意识的短暂变化）至严重（例如，延长的无意识、延长的健忘症、改变的认知功能）。脑部创伤是最有可能导致死亡或永久残疾的损伤类型。TBI的成本， 无论以任何标准衡量，我们的社会都是庞大的。在一般人群中，TBI的风险在整个生命周期中相当恒定，但军事人员的风险要高得多。事实上，创伤性脑损伤已经成为在阿富汗和伊拉克服役的士兵和海军陆战队员所遭受的“标志性”伤害，占所有战斗伤亡的30%左右。据估计，目前冲突中10-20%的退伍军人（150，000 - 300，000）患有某种形式的TBI。TBI被最准确地归类为多发性创伤，因为多个器官系统可以改变。更重要的是，即使是轻微的TBI的影响是累积的，可以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病。药物滥用和酒精滥用，特别是，是一个主要的复杂因素，在TBI，也应该被视为一个共同发生的条件本身。酗酒在现役军人中稳步增加，长期以来一直是退伍军人的严重困扰。像TBI一样，酒精滥用会对CNS造成损害，但对酒精如何影响TBI的严重程度和结果知之甚少。认识到酒精滥用和TBI的风险和后果是双向相关的，本申请的研究目标是更好地了解这两种情况如何相互作用，以确定长期结果。为了实现这一目标，具体目标1将分析TBI之前的酗酒如何改变脑损伤的主要体征和症状，包括水肿，灌注不足，炎症增加，神经元损伤和认知能力下降。具体目标2将评估这些相同的结果措施时，酗酒治疗后TBI。具体目标3将确定TBI是否随后增加酒精的自愿摄入。我们将使用经验证的闭合性头部损伤和酗酒的小鼠模型来实现本申请的目标。

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.