Blast and Blunt Mechanisms for Mild-TBI Induce Differing Outcomes

轻度 TBI 的爆炸和钝器机制会导致不同的结果

• 批准号: 8003003
• 负责人: FRANK A PINTAR
• 金额: --
• 依托单位: CLEMENT J. ZABLOCKI VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003003
• 关键词: Acceleration; Acute; Afghanistan; Aggressive behavior; Amnesia; Animals; Anterograde Amnesia; Anxiety; Applications Grants; Area; Basic Science; Behavior; Behavioral; Blast Cell; Blast Injuries; Blunt Trauma; Body Regions; Brain; Brain Concussion; Brain Edema; Cervical spine; Characteristics; Chronic; Clinical; Cognitive; Comprehensive Health Care; Conflict (Psychology); Conscious; Control Groups; Craniocerebral Trauma; Custom; Data; Data Reporting; Devices; Diagnosis; Disorientation; Emotional; Equipment; Event; Experimental Animal Model; Fatigue; Foundations; Functional disorder; Goals; Head; Headache; Health system; Incidence; Injury; Iraq; Knowledge; Laboratories; Lead; Learning; Life; Literature; Measures; Mechanics; Memory Loss; Mental Depression; Methods; Mild Concussions; Military Personnel; Minor; Modeling; Motor; Motor Vehicles; Nature; Neurologic; Neurologist; Neurons; Neurosurgeon; Operative Surgical Procedures; Outcome; Outcome Measure; Outcome Study; Pathology; Patients; Physics; Physiological; Population; Post-Traumatic Stress Disorders; Protocols documentation; Psychiatrist; Rattus; Rehabilitation therapy; Reporting; Research; Retrograde amnesia; Rodent; Rodent Model; Rotation; Sample Size; Severe Concussions; Severities; Shock; Soldier; Specialist; Spinal Injuries; Sprague-Dawley Rats; Subgroup; Symptoms; Testing; Time; Tissues; Trauma; Traumatic Brain Injury; Tube; Unconscious State; Veterans; War; Work; base; brain tissue; cranium; design; effective therapy; emotional distress; falls; in vivo; injured; memory retention; nerve injury; pressure; rehabilitation strategy; white matter

DESCRIPTION (provided by applicant): ABSTRACT The Department of Veteran's Affairs Health System provides comprehensive health care for veterans returning from conflicts. The incidence of blast traumatic brain injury (TBI) for U.S. veterans has risen considerably since the beginning of the current conflicts in Iraq and Afghanistan. Where injured veterans from previous military conflicts demonstrated primarily focal injuries, a majority of injuries sustained in the current conflicts are blast-induced and are multifocal and polytraumatic in nature. While outcomes from blast TBI are acutely similar to TBI resulting from head impact, a condition commonly sustained during automotive collisions and falls, chronic outcomes may be different. This may indicate a need for Veteran's Affairs clinicians to distinguish between blast and blunt TBI in terms of treatment and rehabilitation. Differences in outcomes between the two mechanisms have not been well defined. The proposed research will incorporate in vivo rodent injury models for blast and blunt trauma mechanisms of TBI to delineate differences in acute, subacute, and chronic outcomes following two levels of mild TBI (i.e., concussion). The blunt trauma injury device induces TBI through pure coronal plane rotational acceleration of the head. The blast injury device induces TBI using a blast overpressure wave created using a compression-driven shock tube. The existing models were developed in our laboratory and are unique in their ability to induce repeatable and recoverable mild TBI without the requirement for invasive surgery. Preliminary testing has demonstrated 100% survivability without cervical spine injury from head rotation or polytrauma typically associated with blast injury. The experimental protocol will expose Sprague Dawley rats to two levels of blast or rotational injury (mild and severe concussion), for a total of five experimental injury groups (including controls). Magnitude of rotational TBI will be modulated by controlling peak head rotational acceleration. Magnitude of blast TBI will be modulated by controlling peak blast overpressure. Injury levels will be equated between the two mechanisms using unconscious times, wherein mean unconscious times will be equal for mild blast and mild rotational TBI and equal for severe blast and severe rotational TBI. Post-injury assessments will incorporate a number of well defined tests to determine the level of anterograde amnesia and spatial learning deficits, retro-grade amnesia, neuromotor deficits, anxiety-related behavior and aggression, adhedonic behavior (i.e., emotionality/depression), brain edema, and neuronal, glial, or white matter pathology. Assessments will be conducted at multiple time points between two and sixty days post-injury. A total of five post-injury assessment sub-groups will be required to avoid confounding effects of different assessments and time points. Therefore, a total of 25 independent groups will be used during the course of the proposed research (five experimental injury groups times five post-injury assessment sub-groups). Statistical analysis using assessment data reported in literature determined a sample size of 15 rats will be required to determine a 1.5-fold or larger difference in the outcome between two treatment groups with 95% confidence. The proposed research will be conducted over a four-year period, with an initial focus on identifying differences between severe blast and severe rotational TBI. Preliminary statistical analyses will be conducted during the course of the proposed research. Pending statistically significant outcomes prior to the completion of all 15 rats per group, other groups (e.g., moderate or super-severe) may be added to the protocol. This research will generate basic science data that will provide the foundation for changes in clinical culture and initiate custom and more effective treatment and rehabilitation protocols for blast and blunt TBI. PUBLIC HEALTH RELEVANCE: NARRATIVE Brain trauma is a major injury resulting from the current conflicts. Returning soldiers that sustained a traumatic brain injury (TBI) undergo rehabilitation and many have lifelong consequences. Of particular difficulty is when the brain trauma is "mild". The symptoms may be headaches, fatigue, and memory loss that are often hard to distinguish and relate to a traumatic event. Soldiers in conflict situations may have been exposed to a blast event or a blunt trauma event related to a head impact. The physics of these injury mechanisms are remarkably different. When these types of injuries are low level or mild, symptoms can be very similar, however the long-term outcomes may be different. This proposal seeks to differentiate between these two types of mild TBI mechanisms by using unique experimental animal models. The rodent models employed will quantify the behavioral and physiological differences, if any, between these two types of TBI. The knowledge gained will serve as a scientific basis for rehabilitation specialists who seek specific treatments for veterans.

描述（由申请人提供）： 摘要退伍军人事务卫生系统部为退伍军人提供了全面的卫生保健。自目前在伊拉克和阿富汗发生冲突以来，美国退伍军人的爆炸创伤性脑损伤（TBI）的发生率大大增加。在先前军事冲突中受伤的退伍军人表现出主要是局部伤害的地方，当前冲突中遭受的大多数伤害都是爆炸引起的，并且本质上是多焦点和多发的。虽然来自BLAST TBI的结果与头部撞击导致的TBI非常相似，这种情况通常在汽车碰撞和跌倒期间持续存在的疾病，但慢性结局可能有所不同。这可能表明需要老兵的事务临床医生在治疗和康复方面区分Blast和Blunt TBI。两种机制之间的结果差异尚未得到很好的定义。拟议的研究将结合TBI的爆炸和钝性创伤机制的体内啮齿动物损伤模型，以描绘两个级别的轻度TBI（即脑震荡），急性，亚急性和慢性结局的差异。钝性创伤装置通过头部的纯冠状平面旋转加速度诱导TBI。爆炸损伤装置使用使用压缩驱动的冲击管产生的爆炸过压波诱导TBI。现有模型是在我们的实验室中开发的，其在无需进行侵入性手术的情况下诱导可重复且可回收的轻度TBI的能力是独一无二的。初步测试表明，没有头部旋转或通常与爆炸损伤相关的多发性颈椎损伤的情况下，没有颈椎损伤。实验方案将使Sprague Dawley大鼠在总共五个实验损伤组（包括对照组）中，将Sprague Dawley大鼠暴露于两个水平的爆炸或旋转损伤（轻度和重度脑震荡）。旋转TBI的大小将通过控制峰头旋转加速度来调节。 BLAST TBI的大小将通过控制峰值爆炸过压来调节。使用无意识的时间，这两种机制之间的损伤水平将等同，其中，对于轻度爆炸和轻度的旋转TBI，无意识的时间将相等，而对于严重的爆炸和严重的旋转TBI，则相当于。伤害后的评估将结合许多定义的测试，以确定顺走失忆和空间学习缺陷的水平，复古级的失忆，神经运动缺陷，与焦虑相关的行为和侵略性，ADHEDONIC行为（即情绪/情绪/抑郁症），脑部经ema和神经元，glial，glial，glial，glial，glial，glial，gliral，gliral，gliral，或白物学。评估将在受伤后两到60天之间的多个时间点进行。总共需要五次伤害后评估子组，以避免不同评估和时间点的混淆影响。因此，在拟议的研究过程中，将共有25个独立组（五个实验损伤组乘以五个伤害后评估子组）。使用文献中报道的评估数据的统计分析确定，将需要15只大鼠的样本量以确定两个治疗组之间的置信度为95％的治疗组之间的结果差异1.5倍或更大。拟议的研究将在四年内进行，最初的重点是确定严重爆炸和严重旋转TBI之间的差异。在拟议的研究过程中，将进行初步统计分析。在完成所有组的所有15只大鼠之前，在统计上有显着的结果，其他组（例如中度或超级严重）可以添加到协议中。这项研究将生成基本科学数据，为临床文化的变化奠定基础，并为BLAST和BLUNT TBI启动习俗，更有效的治疗和康复方案。 公共卫生相关性： 叙事性脑创伤是由于当前冲突而造成的重大伤害。遭受创伤性脑损伤（TBI）的返回士兵经历了康复，许多士兵会带来终生后果。特别困难的是脑外伤是“轻度”的。症状可能是头痛，疲劳和记忆力丧失，通常很难区分并与创伤事件有关。冲突情况下的士兵可能已经暴露于爆炸事件或与头部影响有关的钝性创伤事件。这些伤害机制的物理学大不相同。当这些类型的损伤水平低或轻度时，症状可能非常相似，但是长期结局可能会有所不同。该提案旨在通过使用独特的实验动物模型来区分这两种类型的轻度TBI机制。所采用的啮齿动物模型将量化这两种类型的TBI之间的行为和生理差异（如果有的话）。获得的知识将成为寻求对退伍军人特定治疗的康复专家的科学基础。