Remote ischemic conditioning as a pre-hospital therapeutic intervention for diffuse traumatic brain injury

远程缺血调理作为弥漫性创伤性脑损伤的院前治疗干预

• 批准号: 9135968
• 负责人: Jordan L Harrison
• 金额: $ 3.95万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-17 至 2018-02-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9135968
• 关键词: Acute; Anesthesia procedures; Animals; Attenuated; Back; Behavioral Assay; Blood; Blood - brain barrier anatomy; Blood Circulation; Blood Pressure; Blood flow; Blood specimen; Brain; Brain Injuries; CD59 Antigen; Cell physiology; Cellular Stress; Cerebral Ischemia; Chronic; Clinical; Cognitive; Conflict (Psychology); Coupled; Diffuse; Electrolytes; Emotional; Event; Family; Fatty Acids; Glial Fibrillary Acidic Protein; Gliosis; Heart Arrest; Histocytochemistry; Histopathology; Hospitals; Hour; Hypersensitivity; Immunoglobulin G; Immunohistochemistry; Individual; Inflammation; Injury; Intervention; Ischemic Preconditioning; Limb structure; Lipids; Lipoxins; Liquid Chromatography; Liquid substance; Measures; Mediator of activation protein; Modality; Modeling; Molecular; Morbidity - disease rate; Motor; Nerve; Nervous System Trauma; Neurologic; Organ; Outcome; Outcome Measure; Oxidative Stress; Oxygen; Pathologic Processes; Pathology; Percussion; Permeability; Posture; Process; Quality of life; Rattus; Reperfusion Therapy; Research; Sensory; Silver; Stroke; Symptoms; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Thigh structure; Time; Tourniquets; Traumatic Brain Injury; Travel; United States; Variant; Vibrissae; Walking; arm; attenuation; base; cognitive function; conditioning; cost effective; falls; functional outcomes; functional restoration; improved; improved outcome; insight; invention; lipoxin A4; morris water maze; neuropathology; pre-clinical; public health relevance; regenerative; tandem mass spectrometry

 DESCRIPTION (provided by applicant): After your arm has fallen asleep from an irregular posture, blood rushes back into the limb and nerves previously deprived of oxygen and electrolytes spontaneously regain function. During this process cellular and molecular processes within the ischemic limb may be producing bioactive restorative and regenerative compounds. Remote ischemic conditioning (RIC) is used to describe the process of transiently impeding blood flow to a limb and has shown to provide protection from subsequent major ischemic events in the brain and other organs. RIC can be achieved through a simple and cost-effective technique of applying a tourniquet to a limb for a pre-determined duration. Pre-clinical animal studies on RIC efficacy have been conducted in models of cardiac arrest and cerebral ischemia in which histopathological and functional outcomes have been improved by either pre-injury or post-injury RIC. Cerebral ischemia and traumatic brain injury (TBI), despite having dissimilar primary pathologies, share common secondary injury processes, including inflammation, oxidative stress, and blood-brain barrier permeability. Based on the pathological processes shared by TBI and cerebral ischemia, in this proposal, we test the hypothesis that remote ischemic conditioning (RIC) restores function following diffuse TBI and examine the potential mechanism of RIC action through a class of small lipids termed specialized pro-resolving mediators (SPMs). Aim 1 compares variations in RIC duration and timing in relation to midline fluid percussion brain injury in the rat. Following TBI and RIC, a battery of behavioral assays will be employed to assess the impact of RIC on attenuating the cognitive, sensory, and motor morbidities associated with TBI over a protracted time course. Aim 2, using the most successful variation of RIC identified in Aim 1, will evaluate the effect of RIC on the histopathological consequences of diffuse TBI. Following TBI and RIC, brains will be assessed for markers of neuropathology, inflammation, oxidative stress, and blood-brain barrier permeability. Aim 2 will provide insight into the potential mechanism(s) through which RIC provides protection from neurological injury. These studies can directly impact the course of understanding and treatment for the estimated 1.7 million traumatic brain injuries that occur annually in the United States. Ultimately, RIC could serve as a fast-acting invention for delivering endogenous restorative and reparative compounds to improve outcome from TBI.

 描述（由申请人提供）：在您的手臂从不规则姿势入睡后，血液回流到肢体，之前缺氧和电解质的神经自发恢复功能。在此过程中，缺血肢体内的细胞和分子过程可能产生生物活性的恢复和再生化合物。远程缺血性调节（RIC）用于描述短暂阻碍血液流向肢体的过程，并已显示可保护大脑和其他器官免受随后的重大缺血事件的影响。RIC可以通过一种简单且具有成本效益的技术来实现，即在预定的持续时间内将止血带应用于肢体。在心脏骤停和脑缺血模型中进行了RIC疗效的临床前动物研究，其中损伤前或损伤后RIC改善了组织病理学和功能结局。脑缺血和创伤性脑损伤（TBI）尽管具有不同的原发性病理，但具有共同的继发性损伤过程，包括炎症、氧化应激和血脑屏障通透性。基于TBI和脑缺血共享的病理过程，在这个建议中，我们测试的假设，即远程缺血性条件反射（RIC）恢复功能后弥漫性TBI和检查RIC行动的潜在机制，通过一类小脂质称为专门的亲解决介质（SPM）。 目的1比较大鼠中线液压脑损伤后RIC持续时间和时间的变化。在TBI和RIC之后，将采用一系列行为测定来评估RIC在延长的时间过程中对减轻与TBI相关的认知、感觉和运动发病率的影响。目标2，使用目标1中确定的最成功的RIC变体，将评估RIC对弥漫性TBI的组织病理学后果的影响。在TBI和RIC之后，将评估大脑的神经病理学、炎症、氧化应激和血脑屏障通透性的标志物。目标2将深入了解RIC提供神经损伤保护的潜在机制。这些研究可以直接影响对美国每年发生的约170万例创伤性脑损伤的理解和治疗过程。最终，RIC可以作为一种快速作用的发明，用于提供内源性恢复和修复化合物，以改善TBI的结果。