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)： 退伍军人事务部卫生系统为从冲突中返回的退伍军人提供全面的医疗保健。自当前伊拉克和阿富汗冲突开始以来，美国退伍军人的冲击波创伤性脑损伤(TBI)的发生率大幅上升。在以往军事冲突中受伤的退伍军人主要表现为局部性受伤，而目前冲突中的大多数受伤是爆炸造成的，具有多处和多处创伤的性质。虽然冲击性脑损伤的结果与头部撞击造成的脑损伤非常相似，但慢性结果可能不同。头部撞击是一种常见的汽车碰撞和跌倒情况。这可能表明退伍军人事务部的临床医生需要在治疗和康复方面区分冲击性和钝性脑外伤。这两个机制之间的结果差异尚未得到很好的界定。这项拟议的研究将纳入冲击波和钝性脑损伤机制的体内啮齿动物损伤模型，以描述两种程度的轻度脑损伤(即脑震荡)在急性、亚急性和慢性结局方面的差异。本实用新型通过头部纯冠状面旋转加速致脑外伤。该冲击伤装置使用由压缩驱动激波管产生的爆炸超压波来诱导TBI。现有的模型是在我们的实验室开发的，其独特之处在于它们能够在不需要侵入性手术的情况下诱导可重复和可恢复的轻度脑损伤。初步测试表明，在没有头部旋转造成的颈椎损伤或通常与爆炸伤相关的多发伤的情况下，存活率为100%。实验方案将使SD大鼠暴露于两种水平的冲击伤或旋转伤(轻度和重度脑震荡)，共五个实验损伤组(包括对照组)。通过控制头部峰值旋转加速度来调节旋转TBI的大小。通过控制最大爆破超压来调整爆破TBI的大小。损伤程度将等同于使用无意识时间的两种机制，其中平均无意识时间对于轻度冲击波和轻度旋转伤是相等的，对于重度冲击波和重度旋转伤是相同的。损伤后评估将包括一些明确的测试，以确定顺行性健忘症和空间学习缺陷、复古健忘症、神经运动缺陷、焦虑相关行为和攻击性、粘连行为(即情绪性/抑郁)、脑水肿以及神经元、神经胶质或脑白质病理的水平。评估将在受伤后2至60天之间的多个时间点进行。将需要总共五个伤害后评估分组，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，总共将使用25个独立的小组(5个实验性伤害组乘以5个伤害后评估小组)。使用文献中报告的评估数据进行的统计分析确定，需要15只大鼠的样本大小来确定两个治疗组之间的结果差异1.5倍或更大，置信度为95%。这项拟议的研究将在四年内进行，最初的重点是确定严重冲击波和严重旋转伤之间的差异。在拟议的研究过程中，将进行初步统计分析。在每组15只大鼠全部完成之前，在统计上有显著结果之前，其他组(例如，中度或超重度)可能会被添加到方案中。这项研究将产生基础科学数据，为改变临床文化提供基础，并启动针对冲击性和钝性脑外伤的定制和更有效的治疗和康复方案。 公共卫生相关性： 叙事性脑损伤是当前冲突造成的一大伤害。遭受创伤性脑损伤(TBI)的回国士兵将接受康复治疗，许多人将产生终身后果。尤其困难的是当大脑创伤是“轻微的”时。症状可能是头痛、疲劳和记忆力丧失，这些通常很难区分，并与创伤性事件有关。在冲突情况下，士兵可能接触到与头部撞击有关的爆炸事件或钝性创伤事件。这些损伤机制的物理机制截然不同。当这些类型的伤害是低水平或轻微时，症状可能非常相似，但长期结果可能不同。这项建议试图通过使用独特的实验动物模型来区分这两种类型的轻度脑损伤机制。所采用的啮齿动物模型将量化这两种类型的脑损伤之间的行为和生理差异(如果有的话)。所获得的知识将为寻求退伍军人具体治疗的康复专家提供科学依据。