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。

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.