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。

• 批准号: 9150562
• 负责人: John A Hossack
• 金额: $ 21.78万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9150562
• 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

 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（由申请人提供）：对多毛的调节作为非药物，神经限量调节方法，肥胖，癫痫，癫痫，炎症，糖尿病，支气管收缩（形成抗慢性阻塞性肺部季节和其他人的抗胆碱能治疗的基础），偏见和其他人的基础）在高血压中，大多数设备都需要手术。 ）在其产生或治疗中，没有重大的药理进展。反射神经免疫途径是通过其传入途径传感炎症的关键连接，并通过激活传出途径（脾帽）传输抗炎线索，从而保留了周围器官的功能几个限制。使用人尺度的超声探针，ii）选择了当前可用的参数以解决完全不同的临床 /实验环境中的研究，这阻止了到达的任何变化，以解决到达的到达参数。提案旨在利用AKI超声技术的专业知识和动物模型来验证双重功能探针，以通过绿色D分辨率进行神经免疫调节的脱节。 AKI的EL，可以通过脉搏超声来衰减，从而激活其他疾病，例如类风湿关节炎，结肠炎，胰腺炎，可用于检查其他疾病中的神经免疫调节机制。