Tailoring ultrasound technology to explore mechanisms of activation of the splenic neuroimmune axis in attenuating acute organ injury.

定制超声技术探索脾神经免疫轴激活减轻急性器官损伤的机制。

基本信息

批准号：
9341636
负责人：
John A Hossack
金额：
$ 5.68万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-19 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9341636
关键词：
Acoustics Acute Acute Renal Failure with Renal Papillary Necrosis Address Afferent Pathways Animal Model Animals Anti-Cholinergics Anti-Inflammatory Agents Anti-inflammatory Area Atherosclerosis Attenuated Bronchoconstriction Characteristics Chronic Kidney Failure Chronic Obstructive Airway Disease Clinical Colitis Critical Illness Critical Pathways Cues Data Denervation Development Devices Diabetes Mellitus Dimensions Disease Economics Efferent Pathways Electronics End stage renal failure Epilepsy Family suidae Focused Ultrasound Frequencies Goals Health Heart Heart failure Hospitalization Human Hypertension Image Immune In Vitro Inflammation Inflammatory Injury Ischemia Kidney Kidney Diseases Ligation Liver Longevity Lung Maintenance Mechanics Mediating Methods Migraine Modality Modeling Molecular Mus Myocardial Infarction Names Nerve Nerve Regeneration Neuroimmunomodulation Neurons Norepinephrine Obesity Operative Surgical Procedures Organ Output Pancreatitis Pathway interactions Patients Peripheral Peripheral Nerves Physiologic pulse Prevention Protocols documentation Public Health Puncture procedure Reflex action Reperfusion Injury Reperfusion Therapy Reporting Research Research Personnel Resolution Rheumatoid Arthritis Rodent Sepsis Sequoia Series Specificity Spleen T-Lymphocyte Technology Testing Therapeutic Time Tissue imaging Tissues Transducers Ultrasonic wave Ultrasonics Ultrasonography United States Vagus nerve structure Variant alpha-bungarotoxin receptor base cholinergic design effective therapy improved in vivo indexing innovation interest mortality neuroregulation novel operation prevent programs protective effect relating to nervous system renal ischemia sound tool

项目摘要

DESCRIPTION (provided by applicant): Modulation of peripheral nerve activity as a nonpharmacological, neuroimmumodulatory approach for heart failure, obesity, epilepsy, inflammation, diabetes, bronchoconstriction (forming the basis of anticholinergic treatment of chronic obstructive pulmonary disease), migraines and others and has also been used in hypertension (renal denervation). Despite demonstrated efficacy, optimal therapeutic approaches and a precise understanding of the underlying mechanisms, continue to remain elusive. Moreover most devices are invasive often requiring surgical procedures. Thus, a noninvasive method to modulate peripheral nerve activity could provide an organ protection has targeted innovative approach to understanding neuroimmunomodulation. Over the last few years, we have concentrated our efforts on the use of focused, pulsed ultrasound to protect kidneys from acute kidney injury (AKI), a major health burden with no major pharmacological advances in its prevention or treatment. We reported a simple ultrasound (US)-based protocol that reduced tissue and systemic inflammation and prevented ischemia-reperfusion injury (IRI) in mice by activating the cholinergic anti-inflammatory pathway (CAP). This reflex neuro-immune pathway is a critical juncture in sensing inflammation through its afferent pathway and transmitting anti-inflammatory cues through activation of an efferent pathway (the splenic CAP) thereby preserving peripheral organ function. There are several limitations to our prior approach: i) the use of a human scale clinical ultrasound probe, ii) the inability to target speciic tissues because of the inappropriate probe dimensions, iii) the highly restricted range of ultrasonic focusing / pulsing parameters. The currently available parameters were chosen to address a narrow range of studies in a completely different clinical / experimental context and this limitation precludes any chance of arriving at optimal parameters for controlling mouse AKI. This multi-PI proposal seeks to leverage the strength of expertise in ultrasound technology (scanner operation, beamshaping and transducer design) and animal models of AKI to develop and validate a dual function ultrasound probe to dissect mechanisms of neuroimmunomodulation with greatly improved resolution. Our new high-versatility, dual function, ultrasound probe will be tailored to have the capability of capturing real-time images immediately before or after the application of therapeutic energy to control neural activity and organ function. We plan to test this device in a well-described inflammatory model of AKI, which can be attenuated through pulsed ultrasound that activates the CAP. Results from our tests in AKI may have significant implications in other diseases such as rheumatoid arthritis, colitis, pancreatitis, myocardial infarction to name a few, and the transducer has broad functionality for examining neuroimmunomodulatory mechanisms in these other diseases.

描述（通过应用提供）：对外周神经活动作为心力衰竭，肥胖，癫痫，癫痫，感染，糖尿病，糖尿病，糖尿病的非药理，神经免疫调节方法的调节（形成抗胆碱能治疗的基础，对慢性阻塞性肺疾病，迁移和其他人（又是hypersive）的使用（rental and Hypersive）（Renal and hypersever）（Renal and hypersever）（Renal and hypersever）（renal and sypersever）（renal sypersever）（renal sypersever）（renal sypersever）（Renal and sypersever）（Renal and syperseption（Renal）。尽管表现出效率，最佳的治疗方法和对基本机制的精确理解，但仍然难以捉摸。而且，大多数设备通常是需要手术程序的侵入性。这是一种无创调节外周神经活动的无创方法，可以提供器官保护，它针对理解神经免疫调节的创新方法。在过去的几年中，我们将精力集中在使用集中的，脉冲超声检查以保护肾脏免受急性肾脏损伤（AKI）的使用，这是一种严重的健康燃烧，没有在预防或治疗方面没有重大的药理进展。我们报道了一种简单的超声（US）基础方案，该方案减少了组织和全身感染，并通过激活胆碱能抗炎途径（CAP）来防止小鼠缺血 - 再灌注损伤（IRI）。这种反射神经免疫途径是通过其传入途径传感感染的关键关头，并通过激活有效途径（脾帽）传输抗炎线索，从而保留外围器官功能。我们先前的方法有几个局限性：i）使用人尺度临床超声探针，ii）由于不适当的探针维度，iii）无法靶向特定组织，ii）超声焦点 /脉冲参数范围很大。选择当前可用的参数是为了在完全不同的临床 /实验环境中解决狭窄的研究，并且这种限制排除了任何用于控制小鼠AKI的最佳参数的机会。该多PI提案旨在利用超声技术（扫描仪操作，梁形和换能器设计）和AKI模型的专业知识的强度，以大大改善分辨率的神经免疫调节机制开发和验证双功能超声探测。我们的新高效率，双重功能，超声探针将被量身定制，以便在应用治疗能量以控制神经活动和器官功能之前或之后立即捕获实时图像。我们计划在AKI的炎症模型中测试该设备，该模型可以通过激活CAP的脉冲超声来减弱。我们在AKI测试中的结果可能对其他疾病具有显着影响，例如类风湿关节炎，结肠炎，胰腺炎，心肌梗死，仅举几例，并且传感器具有广泛的功能，可检查其他疾病中神经免疫性机制。