Poly-trauma following brain injury: towards a combinatorial therapy

描述(由申请人提供)： 摘要多项基础科学和临床证据表明，创伤性脑损伤(TBI)的特点是多种病理因素共同作用，最终导致颅脑损伤患者的神经和认知功能障碍。科学家和临床医生一致认为，由于缺乏关于共同病理如何影响结果的基础知识，恢复脑外伤患者的努力受到了限制。此外，到目前为止，还没有人测试针对“多发性创伤”(即治疗头部创伤后发生的事件的多种后遗症)的治疗方法。因此，我们试图调查血管和神经元损伤在脑外伤后不良预后中的作用。总体假设是血管破坏和神经元损伤协同作用导致颅脑损伤后认知功能障碍。这一建议的具体研究目标是：1)表征脑损伤后神经元和血管的反应；2)确定血管改变和/或神经元损伤对认知结果的贡献；3)测试改善血管和神经功能缺陷对神经/行为结果的影响。这项提议最终测试了新的方法，通过改善脑血流和减少继发性神经元损伤来改善脑损伤后的行为结果。在这样做的过程中，我们的目标是制定更有效的战略，以恢复那些已经遭受脑外伤的人。 公共卫生相关性： 项目简介我们许多参加反恐战争的男男女女已经或将遭受头部创伤。由于缺乏对共病的研究，开发减轻脑外伤有害影响的策略的努力受到了限制。因此，这项建议试图了解低灌注率与细胞损伤如何导致认知缺陷。此外，在这样做的过程中，这项建议的目的是制定在创伤性脑损伤后给予的改善结果的战略，这将有助于那些已经遭受伤害的人的康复。由于这两种药物治疗在临床上都具有相关性，我们预计将迅速从“板凳”过渡到床边，从而最大限度地提高从伊拉克和阿富汗回国的人的生活质量。鉴于所有研究人员在脑外伤研究方面的共同经验，预计我们将能够提供更有效的方法来治疗脑损伤后症状(例如神经和认知障碍)，以便更有效地康复我们的服役人员，以恢复头部创伤后的功能和生活质量。

DESCRIPTION (provided by applicant): Abstract Multiple basic science and clinical lines of evidence suggest that traumatic brain injury (TBI) is characterized by several pathologies that combine to ultimately cause neurological and cognitive deficits in those that sustain head injury. Scientists and clinicians, alike, agree that efforts to rehabilitate those suffering from TBI have been curtailed by a lack of fundamental knowledge on how co-pathology contributes to outcome. Furthermore, to date no one has tested therapies aimed at "poly-trauma" (i.e., treating the multiple sequelae of events that occurs following head trauma). Therefore, we seek to investigate the contribution of both vascular and neuronal injury to poor outcome following TBI. The overall hypothesis is that vascular disruption and neuronal injury synergistically contribute to poor cognitive outcome following TBI. The specific research objectives of this proposal are to 1) characterize the neuronal and vascular response to TBI, 2) determine the contribution of vascular changes and/or neuronal injury on cognitive outcome and, 3) test the effect of improving both the vascular and neurologic deficits on neurological/behavioral outcome. This proposal ultimately tests new methods to improve behavioral outcome following TBI by improving blood flow to the brain and reducing secondary neuronal injury. In doing so, we aim to develop more effective strategies to rehabilitate those that have already sustained TBI. PUBLIC HEALTH RELEVANCE: Project Narrative Many of our men and women participating in The War on Terrorism have or will sustain head trauma. Efforts to develop strategies for ameliorating the deleterious effects of TBI have been curtailed by a lack of investigations into co-pathologies. Therefore, this proposal seeks to understand how hypoperfusion combined with cellular damage could lead to cognitive deficits. Furthermore, in doing so, this proposal aims to develop strategies to be given post TBI for improving outcome which will help to rehabilitate those how have already sustained an injury. Since both drug treatments are clinically relevant, we anticipate a quick transition from "bench to bedside", thus maximizing our ability to improve the quality of life of those returning from Iraq and Afghanistan. Given the combined experience of all investigators in TBI research, it is expected that we will be able to deliver more effective means of treating post-TBI symptoms (e.g., neurologic and cognitive deficits) in order to more efficiently rehabilitate our service men and women to regain function and quality of life following head trauma.